Granulocytes from chronic myeloid leukemia (CML) patients show differential response to different chemottractants

Abstract

Binding of chemoattractant to polymorphonuclear leukocytes (PMNL) triggers a series of events like polymerization of actin and tubulin, orientation of cells, chemotaxis, increase in fluid pinocytosis and phagocytosis, and stimulation of microbicidal pathways which includes lysosomal degranulation and generation of reactive oxygen species. Earlier studies from our laboratory have shown that stimulation of chemotaxis, fluid pinocytosis, and actin polymerization of CML PMNL in response to a synthetic chemotactic peptide formyl-methionyl-leucyl-phenylalanine (fMLP) is significantly lower than that in normal PMNL. It is not known whether this lower response of CML PMNL to fMLP is a global phenomenon involving different chemoattractant receptors or is restricted to the fMLP pathway. We have evaluated chemoattractant induced degranulation process in normal and CML PMNL to fMLP, platelet activating factor (PAF), leukotriene B 4 (LTB 4), and an analogue of fMLP viz formyl-methionine-1aminocyclooctane 1 carboxylic acid-phenylalanine-O-methionine (FACC 8) using release of lysozyme as a parameter. We find that after stimulation with fMLP and FACC 8, the mean percent release of lysozyme was significantly lower in CML PMNL as compared to that in normal cells (P < 0.001). There was no significant difference between the two after stimulation with PAF and LTB 4. The results indicate that the fMLP pathway is suppressed in CML granulocytes whereas PAF and LTB 4 pathways appear unaltered in these cells. We therefore also studied the kinetics of peptidereceptor interaction with a labelled hexapeptide fNLPNTL which binds to the fMLP receptor. Our results show that the number of fMLP receptors/cell is significantly lower in CML PMNL (P < 0.05) than in normal PMNL, while their affinity constants and dissociation constants were comparable.