Leucokinin, the specific y-globulin that coats the blood leucocytes and is necessary for its phagocytic activity, becomes inactive following splenectomy. It is devoid of any stimulatory effect on phagocytosis. However, the leucocyte is unimpaired. It exhibits maximal stimulation when coated with active leucokinin obtained before removal of the spleen. The level of erythrophilic y-globulin cellulose phosphate fraction 111 in serum T he physiological role of y-globulin proposed earlier (Najjar, 1963) has been supported by recent findings. It was shown that in the blood of man and dog, the erythrocytes and leucocytes possess membrane-bound yglobulin coats. The type of y-globulin is quite specific to the particular cell. The erythrophilic y-globulin which binds to the membrane of the red cell is necessary for the integrity and normal survival of the cell (Najjar ef al., 1967; Fidalgo et al., 1967a,b). It has not been determined whether leucophilic y-globulin that binds to the membrane of the white blood cell, is necessary for its normal survival. However, it was shown that the bound y-globulin, which has been termed leucokinin, is necessary for the attainment of maximum in uitro phagocytic activity of the polymorphonuclear leucocyte of the dog (Fidalgo and Najjar, 1967a) and man .Within 4-8 weeks following splenectomy in the dog, the main serum y-globulin fraction that binds to the erythrocytes, erythrophilic y-globulin, is considerably decreased. Concomitantly, there is also a marked reduction of the half-life of the red cell reaching, in some instances, a level about 50% of the normal value. Several months after splenectomy, there follows a gradual increase of this fraction approaching normal values between the 4th and 8th month. At the same time, the halflife of the red cell also approaches normal values. The main purpose of this paper is to show that 4-8 weeks is considerably reduced with a parallel reduction of the half-life of the red cell. This is in agreement with a similar study reported earlier. Supplementation of both y-globulins by weekly intramuscular injections results in the complete maintenance of normal leucokinin activity, normal level of erythrophilic y-globulin, and normal erythrocyte half-life.following splenectomy, the stimulatory activity of leucokinin on the phagocytic ability of the leucocyte virtually disappears. The leucokinin activity finally reappears and reaches normal values several months after splenectomy. The levels of the erythrophilic y-globulin and the half-life of the erythrocyte were also followed. The results confirm the previous findings of a parallel reduction of this fraction of y-globulin and of the erythrocyte half-life with subsequent simultaneous recovery. Materials and MethodsMongrel dogs of both sexes weighing 18-25 kg were employed. Splenectomy was performed in the usual manner under strict surgical technic. Blood cultures for Bartonella were taken routinely one to two times monthly and prophylactic procaine penicillin 1 X lo6

No abstract

Chromatography of human 7-globulin on cellulose phosphate columns yielded four distinct fractions, I-IV. The amino acid analyses of the fractions show remarkable similarities though differences do exist.The technique is simple and reproducible. 7-Globulin A (7A) was confined to fraction I and 7globulin M (7M) to fraction II, both as minor com-T A he physiological effect of 7-globulin on autologous blood cells has been demonstrated recently in the dog. It was shown that a specific leucophilic 7-globulin that binds to autologous leucocytes considerably stimulates the phagocytic activity of the cell against pathogenic Staphylococcus aureus (Fidalgo and Najjar, 1967a,b). In its absence, only minimal phagocytosis occurs.

No abstract

During the past decade a series of investigations in this laboratory, dealing with the mechanism of antibody-antigen interaction, led to a new concept proposed by Najjar in 1963:1 that the lymphoid system plays a physiological role with the primary purpose of producing specific y-globulins that bind to complementary receptor sites on the cellular membrane. These proteins are presumed to be necessary for its structural integrity and function, and therefore for the physiology and survival of the cell. The elaboration of antibody by the same lymphoid tissue is nevertheless an important major function and would be an expression of essentially the same phenomenon in response to the intrusion of an unfamiliar and antigenic molecule.1-3 In this respect, this phenomenon would be similar to the detoxification function of the liver: for example, acetylation, methylation, glucuronidation, sulfation, etc. At one time these were believed to be specialized functions that neutralized extraneous toxic amines, phenols, alcohols, etc. All have since been recognized as manifestations of essential biochemical reactions ordinarily engaged in the normal metabolic process and, like antibody formation, serve an important defensive function. This and a recent report4 present evidence in favor of the theory that specific 7y-globulins play a physiological role essential to the normal function of the cellular elements of the blood, the leucocyte, and the erythrocyte.The validity of this theory rests primarily on (a) the demonstration that serum 'y-globulin binds to the autologous cell membrane in a specific manner and (b) that in so doing, it affects favorably one or more functions of the cell. To that end, it was shown that only certain fractions of 7-globulin bind tightly and specifically to autologous red cell membrane in situ and under isotonic conditions of low ionic strength.4-6 Under these conditions, the bound 7y-globulin strengthens the membrane against shearing forces and prevents the rapid fall of the internal ionic concentration of the cell in hypotonic media.5This report is concerned with a particular fraction, leucophilic 7-globulin fraction IV, which is isolated by cellulose phosphate (CP) chromatography, which binds specifically to autologous blood leucocytes, and stimulates phagocytosis of Staphylococcus aureus almost to the full extent observed in normal autologous serum. An earlier communication that appeared in a previous issue of this journal was concerned with an erythrophilic a-globulin, primarily CP fraction III, which binds specifically to red blood cells and appears to be necessary for the normal survival of the cell.4Materials and Methods.-The various serum and cell components were obtained from normal healthy mongrel dogs of both sexes weighing 12-15 kg. As anticoagulant, citrate and glucose were added at a final concentration of 1.6 X 10-2 M each at pH 7.4. Saline (0.15 N NaCl) was used unbuffered. Hank's solution (medium)7 was used throughout with MgCl2 5 X 10-3 M at pH 7.4. The sucrose solution (medium), like ...