Leukocyte function

Johansen, K.S., Berger, E.M., Repine, J.E. (1983). Effect of temperature on polymorphonuclear leukocyte function. Acta Pathol. Microbiol. Immunol. Scand. Sect C, Immunol. 91, 355-359. 

Park BH, Lee TP. 1978. Effects of pesticides on human leukocyte function. In Asher IM, ed., Proc 4th FDA Science Symposium, Annapolis, MD 273-274. 

Molin, L. and Stendahl, O. (1979). The effect of sulfasalazine and its active components on human polymorphonuclear leukocyte function in relation to ulcerative colitis. Acta Med. Scand. 206, 451-457. 

Doll, N.J., Stankus, R.P., Goldbach, S. and Salvaggio, J.E. (1982). In vitro effect of asbestos fibers on polymorphonuclear leukocyte function. Int. Arch. Allergy Appl. Immunol. 68, 17-21. 

Finally, persons with diabetes have altered immune function that predisposes them to infection. Although their humoral immune responses remain intact, leukocyte function and cell-mediated immunity are compromised in poorly controlled disease. Achieving and maintaining tightly controlled blood glucose levels can wholly or partially reverse diabetic immunopathy. 

Inamura, N., Mekori, Y.A., Bhattacharyya, S.P., Bianchine, P.J. and Metcalfe, D.D. (1998) Induction and enhancement of FcERI-dependent mast cell degranulation following coculture with activated T cells dependency on ICAM-1- and leukocyte function-associated antigen (LFA)-l-mediated heterotypic aggregation. Journal of Immunology 160, 4026-4033. 

Ex vivo studies have revealed that trichothecenes can both inhibit and stimulate leukocyte function.12 For example, trichothecenes are toxic to alveolar macrophages,13 but drive differentiation of human myeloid leukemic cells.14 Dose-dependent decreases or increases in B- and T-cell mitogen responses are observable in lymphocytes from animals exposed to T-2 toxin, DON, or various macrocyclic trichothecenes these toxins similarly impair or enhance mitogen-induced lymphocyte proliferation in vitro.12 Rank order of inhibitor potency in rodent and human lymphocyte proliferation assays is Type D > Type A group > Type B group and is dependent on degree of acylation as well as of uptake and metabolism. 

Exposure to trichothecenes at levels that partially inhibit translation upregulates expression of many inflammatory and immune-related genes including macrophage, Thl and Th2 cytokines as well as chemokines, cyclooxygenase 2 and inducible nitric oxide synthase.1518 Contrastingly, suppressive effects of trichothecenes on leukocyte function are intimately linked with the induction of apoptosis as has been demonstrated in macrophages, T cells and B cells both in vivo and in vitro.19-20... 

E. Th. Rietschel, C. Galanos, O. Luderitz, and O. Westphal, in D. R. Webb. (Ed.), Immunopharmacology and the Regulation of Leukocyte Function The Chemistry and Biology of Lipopolysaccharides and Their Lipid A Component, p. 183. Dekker, New York/Basel, 1982. 

Lee TP, Moscati R, Park BH. 1979. Effects of pesticides on human leukocyte functions. Res Comm in Chem Pathol and Pharmacol 23(3) 597-609. 

Pakianathan DR. Extracellular-matrix proteins and leukocyte function. J Leukocyte Biol 1995 57 699-702. 

Stossel, T. P. (1973) Evaluation of opsonic and leukocyte function with a speclrophoto-metric test in patients with infection and with phagocytic disorders. Blood 42,121-130. 

In this chapter we focus on selected aspects of platelet and leukocyte function and dysfunction to illustrate important biochemical pathways. Our approach is not comprehensive, but rather illustrates the complexity of biochemical pathways regulating platelet and leukocyte function in health and disease. 

Selected adhesion molecules represent yet another antibody target. Adhesion molecules, such as LFA-1 (leukocyte function-associated antigen-1) and ICAM-1 (intercellular adhesion molecule 1), play central roles in promoting migration of inflammatory cells to the sites of damage. Such activities underlie many of the symptoms of conditions such as rheumatoid arthritis. Inhibition of adhesion molecule function by administration of antibodies raised against them may, therefore, demonstrate therapeutic potential in some instances. 

Interferons (IFN)—cytokines that modulate ( interfere with) leukocyte function... 

In addition to their effects on leukocyte function, glucocorticoids influence the inflammatory response by reducing the prostaglandin, leukotriene, and platelet-activating factor synthesis that results from activation of phospholipase - Finally, glucocorticoids reduce expression... 

The synthetic analogs of cortisol are useful in the treatment of a diverse group of diseases unrelated to any known disturbance of adrenal function (Table 39-2). The usefulness of corticosteroids in these disorders is a function of their ability to suppress inflammatory and immune responses and to alter leukocyte function, as previously described and as described in Chapter 55. These agents are useful in disorders in which host response is the cause of the major manifestations of the disease. In instances in which the inflammatory or immune response is important in controlling the pathologic process, therapy with corticosteroids may be dangerous but justified to prevent irreparable damage from an inflammatory response—if used in conjunction with specific therapy for the disease process. 

LFA Leukocyte function-associated antigen MAB Monoclonal antibody MHC Major histocompatibility complex NK cell Natural killer cell... 

Alefacept (Amevive) is an immunosuppressive dimeric fusion protein that consists of the extracellular CD2-binding portion of the human leukocyte function antigen-3 linked to the Fc portion of human IgG]. Alefacept interferes with lymphocyte... 

Efalizumab is a humanized IgGlK antibody produced by recombinant DNA technology. It exhibits immunosuppressive function. It binds to CDlla, which is the a-subunit of leukocyte function antigen (LFA)-l. Efalizumab decreases the cell... 

Rotondo S, Rajtar G, Manarini S, Celardo A, Rotillo D, de Gaetano G, Evangelista V, Cerletti C. 1998. Effect of trans-resveratrol, a natural polyphenolic compound, on human polymorphonuclear leukocyte function. Br J Pharmacol 123 1691-1699. 

The ability of NOE matching to identify the correct pose from a collection of decoy poses was demonstrated on three test cases involving lead-like compounds bound to small proteins. One of these test cases involves muscle fatty acid-binding protein (mFABP) and the other two involve the leukocyte function-associated antigen 11-domain (LFA-1). As these results have been presented in detail elsewhere,1151 here we only summarize the results obtained when the BMRB average chemical shifts (diamagnetic protein statistics) were used for chemical shift predictions. The compounds used for these test cases are shown in Scheme 5.1 (compound 3 contains a proprietary core, which is represented by an ellipse). 

The direct effects opioid and opioidlike peptides exhibit on cells of the immune system is both varied and, in some instances, contradictory, depending on which receptor subtype is being studied. Mu and kappa receptors generally affect immunofunction in a suppressive manner, where delta receptors tend to express immunostimulation [82-85]. However, selected delta antagonists have shown to elicit suppressive effects on B-cell proliferation, NK cell activity, and T-helper cell cytokine production [86]. The alteration of leukocyte function via opioid receptors will be discussed highlighting specific cell subtype immunomodulation. Endorphin shows a inhibitory effect on splenocyte proliferation through central and peripheral autocrine/paracrine pathways [87]. 

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