Chemokinesins and chemotaxins of leukocytes and inflamed tissues

Claim 2

Leukocyte derived chemokinesins and chemotaxins, characterized by the following properties: (a) biological activities in vivo and in vitro: selective reversible influence on the motility of leukocytes (chemokinesis) or selective chemical attraction of leukocytes (chemotaxis) in vitro; (b) physico-chemical properties: soluble in aqueous media including in 15% ethanol at a pH value of at least 4.0 to 10; insoluble in ammonium sulfate solution at 90% saturation (3.6 mol/l) electrophoretic migration in acrylaminde matrices at a pH of 7.40 is anodic. they adsorb reversibly in structure and biological activity on anion and cation exchangers, calcium phosphate gel and hydroxyapatite and can be subjected in native form to volume partition chromatography.

Claim 3

Chemokinesins according to claims 1, characterized in that they reversibly lower the motility (statistical cell locomotion) of the leukocytes (negative chemokinesis=apochemokinesis).

Claim 4

Chemokinesin (lymphocyto-monoapakinesin) according to claim 2, characterized in that it is obtainable from lymphocytes and possesses the following additional properties: (a) biological effects: specific reversible lowering of the motility of macrophages (monocytes) in vitro; effective threshold dose in vitro: -2 nmol/l; (b) physico-chemical properties: molecular weight of the native protein (primary structure): approximately 14,000 dalton; absorption spectrum (UV, visible and near IR-range) as given in FIG. 1; extinction coefficients according to the following Table I: TABLE I ______________________________________ Wave length, nm E.sub.1 mg/ml, 1 cm (H.sbsb.2.sub.O, 20° C.) + ______________________________________ 6% 248 (min) 0.43 260 0.59 277 (max) 0.86 280 0.84 290 0.47 400-1000 0 E.sub.280 /E.sub.260 1.42 ______________________________________

Claim 5

Chemokinesin (monocyto-granuloapokinesin) according to claim 2, characterized in that it is obtainable from mononuclear leukocytes and possesses the following additional properties: (a) biological activities: specific reversible lowering of the motility of granulocytes in vitro; effective threshold dose in vitro; <1 nmol/l; (b) physico-chemical properties: molecular weight of the native protein (primary structure): approximately 9,000 dalton; no protein quaternary structure in the form of physically bound peptide subunits: each of the native proteins consists of only one peptide unit; constant temperature coefficient of solubility in ammonium sulfate solutions between -10° C. and +50° C.; absorption spectrum (UV, visible and near IR-range) according to FIG. 2; extinction coefficient according to the following Table II: TABLE II ______________________________________ Wave length, nm E.sub.1 mg/ml, 1 cm (H.sbsb.2.sub.O, 20° C.) + ______________________________________ 6% 249 (min) 0.39 260 0.48 278 (max) 0.71 280 0.70 290 0.48 400-1000 0 E.sub.280 /E.sub.260 1.45 ______________________________________

Claim 6

Chemokinesins according to claims 1, characterized in that they reversibly increase the motility (statistical cell locomotion) of the leukocytes (positive chemokinesis=proschemokinesis).

Claim 7

Chemokinesin (monocyto-granuloproskinesin) according to claim 5, characterized in that it is obtainable from mononuclear leukocytes and possesses the following additional properties: (a) biological activities: specific reversible increase of the motility of granulocytes in vitro; effective threshold dose in vitro: <2 nmol/l; (b) physico-chemical properties: molecular weight of the native protein (primary structure): approximately 16,000 dalton; absorption spectrum (UV, visible and near IR-range) as given in FIG. 3; extinction coefficient according to the following Table III: TABLE III ______________________________________ Wave length, nm E.sub.1 mg/ml, 1 cm (H.sbsb.2.sub.O, 20° C.) + ______________________________________ 6% 251 (min) 0.36 260 0.42 278 (max) 0.56 280 0.54 290 0.35 400-1000 0 E.sub.280 /E.sub.260 1.29 ______________________________________

Claim 8

Chemokinesin (lymphocyto-monoproskinesin) according to claim 5, characterized in that it is obtainable from lymphocytes and possesses the following additional properties: (a) biological activities: specific increase of the motility of macrophages (monocytes) in vitro; effective threshold dose in vitro: <10 nmol/l; (b) physico-chemical properties: molecular weight of the native protein (primary structure): approximately 22,000 dalton; adsorption spectrum (UV, visible and near IR-range) as given in FIG. 4; extinction coefficient according to the following Table IV: TABLE IV ______________________________________ Wave length, nm E.sub.1 mg/ml, 1 cm (H.sbsb.2.sub.O, 20° C.) + ______________________________________ 6% 249 (min) 0.29 260 0.40 279 (max) 0.65 280 0.65 290 0.49 400-1000 0 E.sub.280 /E.sub.260 1.62 ______________________________________

Claim 9

Chemotaxins according to claims 1, characterized in that they chemically attract leukocytes and produce a directed cell migration along their concentration gradient (chemotaxis).

Claim 10

Chemotaxin (monocyto-granulotaxin) according to claim 8, characterized in that it is obtainable from mononuclear leukocytes and possesses the following additional properties: (a) biological activities: chemical attraction of neutrophilic granulocytes in vitro; accumulation of neutrophilic leukocytes in situ with indirect cell-induced angiogenesis and inflammation reaction; effective threshold dose in vitro: <0.5 nmol/l; (b) physico-chemical properties: molecular weight of the native protein (primary structure): approximately 11,000 dalton; absorption spectrum (UV visible and near IR-range) as given in FIG. 5; extinction coefficient according to the following Table V: TABLE V ______________________________________ Wave length, nm E.sub.1 mg/ml, 1 cm (H.sbsb.2.sub.O, 20° C.) + ______________________________________ 6% 253 (min) 0.51 260 0.54 278 (max) 0.66 280 0.66 290 0.54 400-1000 0 E.sub.280 /E.sub.260 1.23 ______________________________________

Claim 11

Chemotaxin (granulocyto-monotaxin) according to claim 8, characterized in that it is obtainable from granulocytes and possesses the following additional properties: (a) biological activities: chemical attraction of macrophages (monocytes) in vitro; accumulation or monocytic leukocytes in situ with indirect, cell-induced angiogenesis and inflammation reaction; effective threshold dose in vitro: <10 nmol/l; (b) physico-chemical properties: molecular weight of the native protein (primary structure): approximately 17,000 dalton; absorption spectrum (UV, visible and near IR-range) as given in FIG. 6; extinction coefficient according to the following Table VI: TABLE VI ______________________________________ Wave length, nm E.sub.1 mg/ml, 1 cm (H.sbsb.2.sub.O, 20° C.) + ______________________________________ 6% 249 (min) 0.36 260 0.43 278 (max) 0.60 280 0.59 290 0.34 400-1000 0 E.sub.280 /E.sub.260 1.37 ______________________________________

Claim 12

Chemotaxin (monocyto-eosinotaxin) according to claim 8, characterized in that it is obtainable from mononuclear leukocytes and possesses the following additional properties: (a) biological activities: chemical attraction of eosinophilic leukocytes in vitro; accumulation of eosinophilic leukocytes in situ; effective threshold dose in vitro; <5 nmol/l; (b) physico-chemical properties: molecular weight of the native protein (primary structure): approximately 5,000 dalton; no protein quaternary structure in the form of physically bound peptide subunits: each of the native proteins consists of only one peptide unit; absorption spectrum (UV, visible and near IR-range) as given in FIG. 7; extinction coefficient according to the following Table VII: TABLE VII ______________________________________ Wave length, nm E.sub.1 mg/ml, 1 cm (H.sbsb.2.sub.O, 20° C.) + ______________________________________ 6% 252 (min) 0.33 260 0.39 277 (max) 0.53 280 0.53 290 0.39 400-1000 0 E.sub.280 /E.sub.260 1.36 ______________________________________

Claim 13

A pharmaceutical composition for specifically influencing the immune system and inflammatory processes of mammalians, comprising an effective amount of at least one leukocyte derived chemokinesin or chemotaxin according to claim 1 and a suitable carrier therefor.

Claim 14

A pharmaceutical composition for specifically influencing the immune system and inflammatory processes of mammalians, comprising an effective amount of at least one leukocyte derived antichemokinesin or chemotaxin immunoglobulin.

Claim 15

A pharmaceutical composition for specifically influencing the immune system and inflammatory processes of mammalians, comprising an effective amount of at least one leukocyte derived antichemokinesin or chemotaxin immunoglobulin.

Claim 16

A method for specifically influencing the immune system and inflammatory processes of mammalians comprising administering an effective amount of at least one leukocyte derived chemokinesin or chemotaxin according to claim 1.

Claim 19

A process for isolating and purifying leukocyte derived chemokinesins and chemotaxins according to claim 1, which comprises: (a) culturing leukocytes in a suitable culture medium; (b) separating said leukocytes from said medium to yield a culture solution; (c) adding a sufficient amount of a suitable salt to precipitate a first protein fraction from said culture solution; (d) separating said first protein portion from said solution; (e) concentrating said solution to obtain a second protein fraction therefrom; (f) separately purifying said first and second protein fractions by molecular sieve filtration, anion and cation exchange chromatography, chromatography on hydroxypapatite, zone precipitation chromatography, or recycling molecular sieve filtration to obtain said chemokinesins.

Claim 20

The process according to claim 16, wherein a mixed leukocyte population is cultured.

Claim 21

The process according to claim 16, wherein a specific leukocyte type is cultured.

Claim 22

The process according to claim 15, wherein the leukocytes are cultured in a fully synthetic cell culture medium containing serum albumin as the only protein.

Claim 23

The process according to claim 15, wherein leukocyte mitosis is induced during the culturing.

Claim 24

The process according to claim 20, wherein a polyvalent mitogen or endotoxin-mitogen is added or an immune reaction is promoted on the cell surface so as to induce the mitosis of the leukocytes.

Claim 25

The process according to claim 21, wherein leukocyte mitosis is induced by the addition of a lectin.

Claim 26

The process according to claim 22, wherein a lectin from Canavalia ensiformis (Concanavalin A=CON) is used.

Claim 27

The process according to claim 19, wherein leukocytes are cultured in a cell culture medium having the composition given in Table VIII.

Claim 28

The process according to claim 24, wherein the leukocytes are cultured for approximately 40 hours at about 37° C. and a concentration of about 10 7 to 10 8 cells/ml culture solution at a CO 2 -partial pressure of about 1% while sufficient oxygen is supplied to the culture.

Claim 29

The process according to claim 25, wherein ammonium sulfate is used for precipitating the proteins.

Claim 30

The process according to claim 26, wherein the ammonium sulfate concentration of the culture solution is stepwise increased and the proteins precipitated after each ammonium sulfate addition are separated, thereby yielding several crude protein fractions having differing solubilities at different ammonium sulfate concentration.

Claim 31

The process according to claim 27, wherein the ammonium sulfate concentration of the culture solution is adjusted stepwise to 35%, 45% and 90% saturation.

Claim 32

The process according to claim 25, wherein the supernatant after separation of the protein precipitate is concentrated by ultrafiltration or dialysis.

Claim 33

The process according to claim 25, wherein at least two of the said purification steps are performed in sequence.

Claim 34

The process according to claim 30, wherein at least three of the said purification steps are performed in sequence.

Claim 35

A process for producing lymphocytomonoapokinesin which comprises: (a) culturing a leukocyte cell population including mixed leukocytes or only lymphocytes; (b) terminating culturing; (c) separating the cells from the culture medium after termination of culturing to yield a culture solution; (d) adding ammonium sulfate to the culture solution up to 90% saturation in order to precipitate proteins contained therein; (e) separating the precipitated proteins from the ammonium sulfate containing supernatant; (f) redissolving the precipitated proteins; (g) purifying said proteins by anion exchange chromatography, preparative molecular sieve filtration, cation exchange chromatography, chromatography on hydroxyapatite, zone precipitation chromatography and recycling molecular sieve filtration; and (h) isolating the lymphocytomonoapokinesin from the eluate of the recycling molecular sieve filtration by adding ammonium sulfate up to about 80-90% saturation and separating the precipitate formed from the supernatant.

Claim 36

A process for producing lymphocytomonoapokinesin which comprises: (a) culturing a leukocyte cell population including mixed leukocytes or only lymphocytes; (b) terminating culturing; (c) separating the cells from the culture medium after termination of culturing to yield a culture solution; (d) adding ammonium sulfate to the culture solution up to 90% saturation in order to precipitate proteins contained therein; (e) separating the precipitated proteins from the ammonium sulfate containing supernatant; (f) redissolving the precipitated proteins; (g) purifying said proteins by anion exchange chromatography, preparative molecular sieve filtration, cation exchange chromatography, chromatography on hydroxyapatite, zone precipitation chromatography and recycling molecular sieve filtration; and (h) isolating the lymphocytomonoapokinesin from the eluate of the recycling molecular sieve filtration by adding ammonium sulfate up to about 80-90% saturation and separating the precipitate formed from the supernatant.

Claim 37

A process for producing highly purified monocytogranuloapokinesin which comprises: (a) culturing a leukocyte cell population containing mixed leukocytes or only monocytes; (b) inducing the mitosis of the cells by CON during culturing; (c) terminating culturing; (d) separating the cells from the culture medium after termination of culturing to yield a culture solution; (e) adding sufficient ammonium sulfate to the culture solution to provide an ammonium sulfate concentration of up to 90% saturation to precipitate proteins contained therein; (f) separating the precipitated proteins from the ammonium sulfate containing supernatant; (g) redissolving the precipitated proteins; (h) purifying said proteins by anion exchange chromatography, preparative molecular sieve filtration, cation exchange chromatography, chromatography on hydroxyapatite, zone precipitation chromatography, and recycling molecular sieve filtration; and (i) isolating the monocytogranuloapokinesin from the eluate of the recycling molecular sieve filtration by adding ammonium sulfate up to about 80-90% saturation and separating the precipitate formed from the supernatant.

Claim 38

A process for producing highly purified monocytogranuloapokinesin which comprises: (a) culturing a leukocyte cell population containing mixed leukocytes or only monocytes; (b) inducing the mitosis of the cells by CON during culturing; (c) terminating culturing; (d) separating the cells from the culture medium after termination of culturing to yield a culture solution; (e) adding sufficient ammonium sulfate to the culture solution to provide an ammonium sulfate concentration of up to 90% saturation to precipitate proteins contained therein; (f) separating the precipitated proteins from the ammonium sulfate containing supernatant; (g) redissolving the precipitated proteins; (h) purifying said proteins by anion exchange chromatography, preparative molecular sieve filtration, cation exchange chromatography, chromatography on hydroxyapatite, zone precipitation chromatography, and recycling molecular sieve filtration; and (i) isolating the monocytogranuloapokinesin from the eluate of the recycling molecular sieve filtration by adding ammonium sulfate up to about 80-90% saturation and separating the precipitate formed from the supernatant.

Claim 39

A process for producing molecularly homogeneous monocytogranuloproskinesin which comprises: (a) culturing a leukocyte cell population containing mixed leukocytes or only monocytes; (b) inducing the mitosis of the cells by CON during culturing; (c) terminating culturing; (d) separating the cells from the culture medium after termination of culturing to form a culture solution; (e) adding ammonium sulfate to the culture solution up to 90% saturation in order to precipitate proteins contained therein; (f) separating the precipitated proteins from the ammonium sulfate containing supernatant; (g) redissolving the precipitated proteins; (h) purifying said proteins by anion exchange chromatography, preparative molecular sieve filtration, cation exchange chromatography, chromatography on hyroxyapatite, zone precipitstion chromatography and recycling molecular sieve filtration; and (i) isolating the monocytogranuloproskinesin from the eluate of the recycling molecular sieve filtration by adding ammonium sulfate up to about 80-90% saturation and separating the precipitate formed from the supernatant.

Claim 40

A process for producing molecularly homogeneous monocytogranuloproskinesin which comprises: (a) culturing a leukocyte cell population containing mixed leukocytes or only monocytes; (b) inducing the mitosis of the cells by CON during culturing; (c) terminating culturing; (d) separating the cells from the culture medium after termination of culturing to form a culture solution; (e) adding ammonium sulfate to the culture solution up to 90% saturation in order to precipitate proteins contained therein; (f) separating the precipitated proteins from the ammonium sulfate containing supernatant; (g) redissolving the precipitated proteins; (h) purifying said proteins by anion exchange chromatography, preparative molecular sieve filtration, cation exchange chromatography, chromatography on hyroxyapatite, zone precipitstion chromatography and recycling molecular sieve filtration; and (i) isolating the monocytogranuloproskinesin from the eluate of the recycling molecular sieve filtration by adding ammonium sulfate up to about 80-90% saturation and separating the precipitate formed from the supernatant.

Claim 41

A process for producing highly purified lymphocytomonoproskinesin which comprises: (a) culturing a leukocyte cell population containing mixed leukocytes or only lymphocytes; (b) inducing the mitosis of the cells by CON during culturing; (c) terminating culturing; (d) separating the cells from the culture medium after termination of culturing to yield a culture solution; (e) adding ammonium sulfate to the culture solution up to 90% saturation to precipitate proteins contained therein; (f) separating the precipitated proteins from the ammonium sulfate containing supernatant; (g) redissolving said precipitated proteins; (h) purifying said proteins by anion exchange chromatography, preparative molecular sieve filtration, cation exchange chromatography, chromatography on hydroxyapatite, zone precipitation chromatography and recycling molecular sieve filtration; and (i) isolating the lympohocytomonoproskinesin from the eluate of the recycling molecuar sieve filtration by adding ammonium sulfate up to about 80-90% saturation and separating the precipitate from the supernatant.

Claim 42

A process for producing highly purified lymphocytomonoproskinesin which comprises: (a) culturing a leukocyte cell population containing mixed leukocytes or only lymphocytes; (b) inducing the mitosis of the cells by CON during culturing; (c) terminating culturing; (d) separating the cells from the culture medium after termination of culturing to yield a culture solution; (e) adding ammonium sulfate to the culture solution up to 90% saturation to precipitate proteins contained therein; (f) separating the precipitated proteins from the ammonium sulfate containing supernatant; (g) redissolving said precipitated proteins; (h) purifying said proteins by anion exchange chromatography, preparative molecular sieve filtration, cation exchange chromatography, chromatography on hydroxyapatite, zone precipitation chromatography and recycling molecular sieve filtration; and (i) isolating the lympohocytomonoproskinesin from the eluate of the recycling molecuar sieve filtration by adding ammonium sulfate up to about 80-90% saturation and separating the precipitate from the supernatant.

Claim 43

A process for producing highly purified monocytogranulotaxin which comprises: (a) culturing a leukocyte cell population containing mixed leukocytes or only monocytes; (b) inducing the mitosis of the cells by CON during culturing; (c) terminating culturing; (d) separating the cells from the culture medium after terminating culturing to yield a culture solution; (e) adding ammonium sulfate to the culture solution up to 90% saturation to precipitate proteins concentrated therein; (f) separating the precipitated proteins from the ammonium sulfate containing supernatant; (g) redissolving said precipitated proteins; (h) purifying said proteins by anion exchange chromatography, preparative molecular sieve filtration, cation exchange chromatography, chromatography on hydroxyapatite, zone prcipitation chromatography and recycling molecular sieve filtration; and (i) isolating the monocytogranulotaxin from the eluate of the recycling molecular sieve filtration by adding ammonium sulfate up to about 80-90% saturation and separating the precipitate formed from the supernatant.

Claim 44

A process for producing highly purified monocytogranulotaxin which comprises: (a) culturing a leukocyte cell population containing mixed leukocytes or only monocytes; (b) inducing the mitosis of the cells by CON during culturing; (c) terminating culturing; (d) separating the cells from the culture medium after terminating culturing to yield a culture solution; (e) adding ammonium sulfate to the culture solution up to 90% saturation to precipitate proteins concentrated therein; (f) separating the precipitated proteins from the ammonium sulfate containing supernatant; (g) redissolving said precipitated proteins; (h) purifying said proteins by anion exchange chromatography, preparative molecular sieve filtration, cation exchange chromatography, chromatography on hydroxyapatite, zone prcipitation chromatography and recycling molecular sieve filtration; and (i) isolating the monocytogranulotaxin from the eluate of the recycling molecular sieve filtration by adding ammonium sulfate up to about 80-90% saturation and separating the precipitate formed from the supernatant.

Claim 45

A process for preparing highly purified granulocytomonotaxin which comprises: (a) culturing a leukocyte cell population containing mixed leukocytes or only granulocytes; (b) inducing the mitosis of the cells by CON during culturing; (c) terminating culturing; (d) separating the cells from the culture medium after terminating culturing to yield a culture solution; (e) adding ammonium sulfate to the culture solution to achieve up to 90% saturation in order to precipitate proteins contained therein; (f) separating the precipitated proteins from the ammonium sulfate containing supernatant; (g) redissolving said proteins; (h) purifying said proteins by anion exchange chromatography, preparative molecular sieve filtration, cation exchange chromatography, chromatography on hydroxyapatite, zone precipitation chromatography and recycling molecular sieve filtration; and (i) isolating the granulocytomonotaxin in highly purified form in the eluate of the recycling molecular sieve filtration by adding ammonium sulfate up to about 80-90% saturation and separating the precipitate formed from the supernatant.

Claim 46

A process for preparing highly purified granulocytomonotaxin which comprises: (a) culturing a leukocyte cell population containing mixed leukocytes or only granulocytes; (b) inducing the mitosis of the cells by CON during culturing; (c) terminating culturing; (d) separating the cells from the culture medium after terminating culturing to yield a culture solution; (e) adding ammonium sulfate to the culture solution to achieve up to 90% saturation in order to precipitate proteins contained therein; (f) separating the precipitated proteins from the ammonium sulfate containing supernatant; (g) redissolving said proteins; (h) purifying said proteins by anion exchange chromatography, preparative molecular sieve filtration, cation exchange chromatography, chromatography on hydroxyapatite, zone precipitation chromatography and recycling molecular sieve filtration; and (i) isolating the granulocytomonotaxin in highly purified form in the eluate of the recycling molecular sieve filtration by adding ammonium sulfate up to about 80-90% saturation and separating the precipitate formed from the supernatant.

Claim 47

A process for producing monocytoeosinotaxin which comprises: (a) culturing a leukocyte cell population containing mixed leukocytes or only monocytes; (b) inducing the mitosis of the cells by CON during culturing; (c) terminating culturing; (d) separating the cells from the culture medium after terminating culturing to yield a culture solution; (e) adding ammonium sulfate to the culture solution to achieve up to a 90% saturation in order to precipitate proteins contained therein; (f) separating the precipitated proteins from the ammonium sulfate containing supernatant; (g) redissolving the precipitated proteins; (h) purifying said proteins by anion exchange chromatography, preparative molecular sieve filtration, cation exchange chromatography, chromatography on hydroxyapatite, zone precipitation chromatography and recycling molecular sieve filtration; and (i) isolating the monocytoeosinotaxin in highly purified form in the eluate of the recycling molecular sieve filtration by adding ammonium sulfate up to about 80-90% saturation and separating the precipitate formed from the supernatant.

Claim 48

A process for producing monocytoeosinotaxin which comprises: (a) culturing a leukocyte cell population containing mixed leukocytes or only monocytes; (b) inducing the mitosis of the cells by CON during culturing; (c) terminating culturing; (d) separating the cells from the culture medium after terminating culturing to yield a culture solution; (e) adding ammonium sulfate to the culture solution to achieve up to a 90% saturation in order to precipitate proteins contained therein; (f) separating the precipitated proteins from the ammonium sulfate containing supernatant; (g) redissolving the precipitated proteins; (h) purifying said proteins by anion exchange chromatography, preparative molecular sieve filtration, cation exchange chromatography, chromatography on hydroxyapatite, zone precipitation chromatography and recycling molecular sieve filtration; and (i) isolating the monocytoeosinotaxin in highly purified form in the eluate of the recycling molecular sieve filtration by adding ammonium sulfate up to about 80-90% saturation and separating the precipitate formed from the supernatant.

Claim 49

The process according to any one of claims 15 and 26 to 38, wherein the soluble portion of a leukocyte or inflamed tissue homogenate is used instead of the culture solution of the leukocytes.

Claim 50

Highly purified lymphocytomonoapokinesin.

Claim 51

Highly purified lymphocytomonoapokinesin.

Claim 52

Highly purified monocytogranuloapokinesin.

Claim 53

Highly purified monocytogranuloapokinesin.

Claim 54

Highly purified monocytogranuloproskinesin.

Claim 55

Highly purified monocytogranuloproskinesin.

Claim 56

Highly purified lymphocytomonoproskinesin.

Claim 57

Highly purified lymphocytomonoproskinesin.

Claim 58

Highly purified monocytogranulotaxin.

Claim 59

Highly purified monocytogranulotaxin.

Claim 60

Highly purified granulocytomonotaxin.

Claim 61

Highly purified granulocytomonotaxin.

Claim 62

Highly purified monocytoeosinotaxin.

Claim 63

Highly purified monocytoeosinotaxin.