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Am J Physiol Heart Circ Physiol 282: H122-H130, 2002;
0363-6135/02 $5.00
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Vol. 282, Issue 1, H122-H130, January 2002

Activated polymorphonuclear cells increase sickle red blood cell retention in lung: role of phospholipids

Johnson Haynes Jr. and Boniface Obiako

Pulmonary and Critical Care Division, Departments of Medicine and Physiology, University of South Alabama College of Medicine, Mobile, Alabama 36688

This study investigates the role of the activated polymorphonuclear cell (APMN) products on sickle red blood cell (SRBC) retention/adherence in the pulmonary circulation. Isolated rat lungs were perfused with 51Cr-labeled normal RBCs (NRBC) or SRBCs (10% hematocrit) suspensions ± PMNs. Specific activities of lung and perfusate were measured and retention (the number of SRBC/g lung) was calculated. SRBC retention was 3.5 times greater than NRBC retention. PMN activation was required to increase SRBC retention. Supernatants from APMN increased SRBC retention, which suggested soluble products such as oxidants, PAF, and/or leukotriene (LTB4) are involved. Heat inactivation of PMN NADPH oxidase had no effect on retention. Whereas neither platelet-activating factor (PAF) nor LTB4 (secreted by APMN) increased SRBC retention, PAF+LTB4 did. The PAF antagonist, WEB-2170, attenuated SRBC retention mediated by PAF+LTB4 and APMNs. Similarly, zileuton (5-lipoxygenase inhibitor) attenuated APMN-mediated SRBC retention. We conclude the concomitant release of PAF and LTB4 from APMN is involved in the initiation of microvascular occlusion by SRBCs in the perfused rat lung.

platelet-activating factor; leukotriene B4; zileuton; WEB-2170


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