BIPOLAR-SHAPE RESPONSE OF HUMAN NEUTROPHILS TO CORTICOTROPIN-RELEASING FACTOR

Human neutrophils in whole blood become bipolar in shape after exposur e to chemokinetic stimuli. In normal blood, the proportion of non-sphe rical neutrophils was 1.2 +/- 0.07% (n = 101). After incubation of blo od samples with corticotropin-releasing hormone (CRF, 1 to 20 mu M) 36 of 101 subjects exhibited a greater than or equal to 10% bipolar-shap e ellipsoid response. This ellipsoid response was more frequent in fem ale than in male subjects (32/75 vs. 4/26, p < 0.01). Female Caucasian subjects were more sensitive to CRF than female East Asian subjects ( 25/48 vs. 2/15, p < 0.01). Age was not a factor in sensitivity to CRF. In young female East Asian subjects (23 +/- 0.4 years, n = 8) that di d not manifest the ellipsoid response to CRF, formyl-Met-Leu-Phe (fMLP ), a chemotactic peptide, 10(-9) M increased non-spherical neutrophils to 31 +/- 0.8%. In these individuals, the fMLP response was inhibited in a dose-dependent manner by CRF. The pharmacological profile of the stimulatory and fMLP-inhibitory actions of CRF on neutrophil shape wa s consistent with that of a CRF1-receptor mediated response. Expressio n of mRNA for the CRF1-receptor was detected in hematopoietic cell fin es (e.g., HL-60) using a reverse transcriptase polymerase chain-reacti on method. The bipolar-shape response of human neutrophils to CRF has the potential to be a useful indicator of the functional state of this hormone-receptor system in inflammation. (C) 1998 Elsevier Science B. V. All rights reserved.