Abstract
Rat neutrophil chemotactic responses to N-formyl-methionyl-leucyl-phenylalanine (FMLP), leukotriene (LT) B4, and lipopolysaccharide-activated serum (LPS-AS) were quantitatively assessed using the micropore filter system. Cells were suspended in either normal or diabetic rat serum for testing. Diabetic donor serum did not affect migration of neutrophils in a concentration gradient of the synthetic chemotactic agents. In contrast, the migratory responses to LPS-AS were significantly less than normal in this circumstance. Summation of effects was observed when FMLP and LPS-AS, or LTB4 and LPS-AS were simultaneously added to the test chamber, with cells suspended in normal serum. Suspended in diabetic rat serum neutrophils responded normally to the synthetic chemoattractants but the response to the activated serum was blocked. Cells previously incubated in the presence of diabetic donor serum then transferred to a culture medium for testing, presented reduced migratory responses to LPS-AS. Supramaximal, inhibitory concentrations of FMLP and LTB4, did not influence the response of neutrophils to LPS-AS.In vivo, suppression of cellular emigration to an inflamed area was observed from the early stages of the diabetic state. The inhibitory activity of chemotaxis in diabetes mellitus was previously reported to be associated with a protein factor in plasma of the animals. It is suggested that the inhibitory factor of chemotaxis in diabetes mellitus interacts with neutrophil receptors for complement-derived chemoattractants to induce blockade of cell-oriented locomotion eitherin vitro orin vivo.
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J. A. Savin,Bacterial infections in diabetes mellitus. Br. J. Dermatol.91, 481–487 (1974).
J. G. Larkin, B. M. Frier and J. Ireland.Diabetes mellitus and infection. Postgrad. Med. J.61, 233–237 (1985).
J. Garcia-Leme,Hormones and Inflammation, 238 pp, CRC Press, Boca Raton 1989.
J. Garcia-Leme, L. Hamamura, R. H. Migliorini and M. P. Leite,Influence of diabetes upon the inflammatory response of the rat: a pharmacological analysis. Eur. J. Pharmacol.23, 74–81 (1973).
J. Garcia-Leme, G. M. Bohm, R. H. Migliorini and M. Z. A. Souza,Possible participation of insulin in the control of vascular permeability. Eur. J. Pharmacol.29, 298–306 (1974).
M. A. S. Llorach, G. M. Bohm and J. Garcia-Leme,Decreased vascular reactions to permeability factors in experimental diabetes. Br. J. Exp. Pathol.57, 747–754 (1976).
B. M. Altura, S. Halevy and P. D. M. V. Turlapaty,Vascular smooth muscle in diabetes and its influence on the reactivity of blood vessels. Adv. Microcircul.8, 118–150 (1979).
Z. B. Fortes, J. Garcia-Leme and R. Scivoletto,Influence of diabetes on the reactivity of mesenteric microvessels to histamine, bradykinin and acetylcholine. Br. J. Pharmacol.78, 39–48 (1983).
Z. B. Fortes, J. Garcia-Leme and R. Scivoletto,Vascular reactivity in diabetes mellitus: role of the endothelial cell. Br. J. Pharmacol.79, 771–781 (1983).
Z. B. Fortes, J. Garcia-Leme and R. Scivoletto,Vascular reactivity in diabetes mellitus: possible role of insulin on the endothelial cell. Br. J. Pharmacol.83, 635–643 (1984).
A. G. Mowat and J. Baum,Chemotaxis of polymorphonuclear leukocytes from patients with diabetes mellitus. N. Engl. J. Med.284, 621–624 (1971).
M. E. Miller and L. Baker,Leukocyte functions in juvenile diabetes mellitus: humoral and cellular aspects. J. Pediatr.81, 979–982 (1972).
H. R. Hill, H. S. Sauls, J. L. Dettloff and P. G. Quie,Impaired leukocyte responsiveness in patients with juvenile diabetes mellitus. Clin. Immunol. Immunopathol.2, 395–403 (1974).
A. E. Mohandes, J. L. Touraine, M. Osman and B. Salle,Neutrophil chemotaxis in infants of diabetic mothers and in preterms at birth. J. Clin. Lab. Immunol.8, 117–120 (1982).
M. A. A. Pereira, P. Sannomiya and J. Garcia-Leme,Inhibition of leukocyte chemotaxis by factor in alloxan-induced diabetic rat plasma. Diabetes36, 1307–1314 (1987).
S. Boyden,The chemotactic effect of mixtures of antibody and antigen on polymorphonuclear leukocytes. J. Exp. Med.15, 453–466 (1962).
S. H. Zigmond and J. G. Hirsch,Leukocyte locomotion and chemotaxis: new method for evaluation and demonstration of cell-derived chemotactic factor. J. Exp. Med.137, 387–410 (1973).
W. G. Spector,The mediation of altered capillary permeability in acute inflammation. J. Pathol. Bacteriol.72, 367–380 (1956).
B. Desbuquois and G. D. Aurbach,Use of polyethylene glycol to separate free and antibody-bound peptide hormones in radioimmunoassays. J. Clin. Endocrinol.33, 732–738 (1971).
P. Sannomiya, H. J. Anteghini, E. S. O. Vianna and J. Garcia-Leme,Involvement of lymphocytes in non-immune inflammation: dual effect of glucocorticoids. Agents and Actions16, 552–557 (1985).
H. V. Showell, R. J. Freer, S. H. Zigmond, E. Schiffmann, S. Aswanikumar, B. Corcoran and E. L. Becker,The structure-activity relations of synthetic peptides as chemotactic factors and inducers of lysosomal ensyme secretion for neutrophils. J. Exp. Med.143, 1154–1169 (1976).
E. J. Goetzl and W. C. Pickett,Novel structural determinants of the human neutrophil chemotactic activity of leukotriene B. J. Exp. Med.153, 482–487 (1981).
C. L. Malmsten, J. Palmblad, A. M. Udén, O. Radmark, L. Engstedt and B. Samuelsson,Leukotriene B4: a highly potent and stereospecific factor stimulating migration of polymorphonuclear leukocytes. Acta Physiol. Scand.110, 449–451 (1980).
M. J. H. Smith, A. W. Ford-Hutchinson and M. A. Bray,Leukotriene B: a potential mediator of inflammation. J. Pharm. Pharmacol.32, 517–518 (1980).
H. S. Shin, R. Snyderman, E. Friedman, A. Mellors and M. M. Mayer,A chemotactic and anaphylatoxic fragment cleaved from guinea pig C′5 by EAC′ 1a, 4, 2a, 3. Science162, 361–363 (1968).
J. A. Jensen, R. Snyderman and S. E. Mergenhagen,Chemotactic activity, a property of guinea pig C′5-anaphylatoxin. InCellular and Humoral Mechanisms of Anaphylaxis and Allergy. (Ed. H. Z. Movat) pp. 265–278, Karger, Basel 1969.
P. A. Ward,The heterogeneity of chemotactic factors for neutrophils generated from the complement system. InCellular and Humoral Mechanisms in Anaphylaxis and Allergy. (Ed. H. Z. Movat) pp. 279–288, Karger, Basel 1969.
P. A. Ward and L. J. Newman,A neutrophil chemotactic factor from human C′5. J. Immunol.102, 93–99 (1969).
L. Pillemer, M. D. Shoenberg, L. Blum and L. Wurz,Properdin system and immunity. II. Interaction of the properdin system with polysaccharides. Science122, 545–549 (1955).
L. H. Muschel, K. Schmoker and P. M. Webb,Anti-complementary actions of endotoxin. Proc. Soc. Exp. Biol. Med.117, 639–643 (1964).
O. Gotze and H. J. Muller-Eberhard,The C3 activator system: an alternate pathway of complement activation. J. Exp. Med. Suppl., vol134, 90–180 (1971).
R. Snyderman and M. C. Pike,Interaction of complex polysaccharides with the complement system: effect of calcium depletion on terminal component consumption. Infect. Immun.11, 273–279 (1975).
D. C. Morrison and L. F. Kline,Activation of the classical and properdin pathways of complement by bacterial lipopolysaccharides (LPS). J. Immunol.118, 362–368 (1977).
R. Snyderman, H. S. Shin, J. K. Phillips, H. Gewurz and S. E. Mergenhagen,A neutrophil chemotactic factor derived from C′5 upon interaction of guinea-pig serum with endotoxin. J. Immunol.103, 413–422 (1969).
S. Aswanikumar, B. Corcoran, E. Schiffmann, A. R. Day, R. J. Freer, H. J. Showell and E. L. Becker,Demonstration of a receptor on rabbit neutrophils for chemotactic peptides. Biochem. Biophys. Res. Commun.74, 810–822 (1977).
L. T. Williams, R. Snyderman, M. C. Pike and R. J. Lefkowitz,Specific receptor site for chemotactic peptides on human polymorphonuclear leukocytes. Proc. Nat. Acad. Sci. USA74, 1204–1208 (1977).
S. J. Sullivan and S. H. Zigmond,Chemotactic peptide modulation in polymorphonuclear leukocytes. J. Cell. Biol.85, 703–711 (1980).
W. A. Marasco, J. C. Fantone, R. J. Freer and P. A. Ward,Characterization of the rat neutrophil formyl peptide chemotaxis receptor. Am J. Pathol.111, 273–281 (1983).
D. W. Goldman and G. J. Goetzl,Specific binding of leukotriene B4 to receptors of human polymorphonuclear leukocytes. J. Immunol.129, 1600–1604 (1982).
R. A. Kreisle and C. W. Parker,Specific binding of leukotriene B4 to a receptor on human polymorphonuclear leukocytes. J. Exp. Med.157, 628–641 (1983).
D. E. Chenoweth and T. E. Hugli,Human C5a and C5a analogs as probes of the neutrophil C5a receptor. Mol. Immunol.17, 151–161 (1980).
G. D. Warden, A. D. Mason, Jr. and B. A. Pruitt, Jr.,Suppression of leukocyte chemotaxis in vitro by chemotherapeutic agents used in the manegement of thermal injuries. Ann. Surg.181, 363–369 (1975).
J. B. Grogan,Suppressed in vitro chemotaxis of burn neutrophils. J. Trauma16, 985–988 (1976).
S. M. Fikrig, S. C. Karl and L. Suntharalingam,Neutrophil chemotaxis in patients with burns. Ann. Surg.186, 746–748 (1977).
J. M. Davis, P. Dineen and J. I. Gallin,Neutrophil degranulation and abnormal chemotaxis after thermal injury. J. Immunol.124, 1467–1471 (1980).
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Sannomiya, P., Pereira, M.A.A. & Garcia-Leme, J. Inhibition of leukocyte chemotaxis by serum factor in diabetes mellitus: Selective depression of cell responses mediated by complement-derived chemoattractants. Agents and Actions 30, 369–376 (1990). https://doi.org/10.1007/BF01966301
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DOI: https://doi.org/10.1007/BF01966301