Human monocyte and polymorphonuclear leukocyte chemotactic and chemokinetic responses to leukotriene B4 and FMLP

Abstract

Comparable investigations of the chemotactic and chemokinetic responses of purified monocytes (MO) and polymorphonuclear leukocytes (PMN) to leukotriene B4 (LTB4) and N-formyl-methionyl-leucyl-phenylalanine (FMLP) were made in this study. Using a sensitive and objective 51Cr-chemotactic assay, it was shown that both MO and PMN showed a bell-shaped response to LTB4 and FMLP, with a maximum response at 10(-8)M for both drugs. For PMN, the maximal response elicited by LTB4 was similar in magnitude to that produced by FMLP, whereas the MO chemotaxis induced by 10(-8)M FMLP was significantly higher than the response evoked by 10(-8)M LTB4. For both cell types, LTB4 at low concentrations (less than 10(-9)M) gave rise to higher chemotactic responses than FMLP. Chemokinesis was differentiated from chemotaxis, using a checkerboard system. At concentrations less than 10(-9)M the LTB4-evoked contribution of chemokinesis to the total migrational response was significantly higher than the chemokinetic contribution of FMLP. Preincubation with LTB4 produced only homologous chemotactic deactivation to subsequent LTB4 stimulation, whereas preincubation with FMLP resulted in diminished secondary response to both FMLP and LTB4. The degree of deactivation was dependent upon the dose of attractant used, with a LTB4 concentration of 10(-7)M leading to about 40% and 25% deactivation of PMN and MO, respectively. Preincubation with 10(-7)M FMLP led to about 50% and 32% suppression of the subsequent chemotactic response of PMN and MO, respectively.