Altered Ca2+ homeostasis in polymorphonuclear leukocytes from chronic myeloid leukaemia patients

Chetana M Revankar,Nishigandha R Naik,Suresh H Advani

doi:10.1186/1476-4598-5-65

Abstract

BackgroundIn polymorphonuclear leukocytes (PMNL), mobilization of calcium ions is one of the early events triggered by binding of chemoattractant to its receptors. Besides chemotaxis, a variety of other functional responses are dependent on calcium ion mobilization. PMNL from chronic myeloid leukaemia (CML) patients that were morphologically indistinguishable from normal PMNL were found to be defective in various functions stimulated by a chemoattractant – fMLP. To study the mechanism underlying defective functions in CML PMNL, we studied calcium mobilization in CML PMNL in response to two different classical chemoattractants, fMLP and C5a.ResultsRelease of calcium estimated by flow cytometry and spectrofluorimetry using fluo-3 as an indicator showed that the [Ca2+]i levels were lower in CML PMNL as compared to those in normal PMNL. But, both normal and CML PMNL showed maximum [Ca2+]i in response to fMLP and C5a at 10 sec and 30 sec, respectively. Spectrofluorimetric analysis of the total calcium release in chemoattractant treated PMNL indicated more and faster efflux of [Ca2+]i in CML PMNL as compared to normal PMNL.ConclusionFine-tuning of Ca2+ homeostasis was altered in CML PMNL. The altered Ca2+ homeostasis may contribute to the defective functions of CML PMNL.

Highlights

In polymorphonuclear leukocytes (PMNL), mobilization of calcium ions is one of the early events triggered by binding of chemoattractant to its receptors
We found that finetuning of Ca2+ homeostasis in chronic myeloid leukaemia (CML) PMNL was altered as compared to that in normal PMNL
Fluo-3 loaded unstimulated CML PMNL showed a broad plot with a long tail near Y-axis, containing 9–10% of the population

Summary

Introduction

In polymorphonuclear leukocytes (PMNL), mobilization of calcium ions is one of the early events triggered by binding of chemoattractant to its receptors. A variety of other functional responses are dependent on calcium ion mobilization. To study the mechanism underlying defective functions in CML PMNL, we studied calcium mobilization in CML PMNL in response to two different classical chemoattractants, fMLP and C5a. In polymorphonuclear leukocytes (PMNL), changes in intracellular calcium, i.e. PMNL migration can be induced by binding of chemoattractants to their receptors present on PMNL surface. The classical chemoattractants for PMNL are nformyl peptides that are analogous to bacterial secretion [4] and anaphylatoxin C5a, which is formed upon com-. Mobilization of [Ca2+]i is one of the early events triggered by binding of a chemoattractant to its receptor

Methods

Results

Conclusion