Sickle erythrocytes adhere to polymorphonuclear neutrophils and activate the neutrophil respiratory burst.

The vasoocclusive process in patients with sickle cell disease (SCD) is complex and involves interactions among sickle erythrocytes (SS-RBC), vascular endothelium, and plasma and cellular components. The role of neutrophils (PMN) in vasoocclusion has not been examined. Patients with SCD appear to have chronically activated PMN. Because the first step in PMN activation is particle recognition, we explored whether normal PMN recognize SS-RBC and whether this recognition results in PMN monolayers, significantly more SS-RBC adhered to the PMN than did normal erythrocytes (AA-RBC; P < .001). Preincubation of erythrocytes with autologous plasma significantly increased the adherence of SS-RBC to PMN but had no effect on AA-RBC (P < .001). When adhesion of density fractionated SS-RBC was performed, dense SS-RBC showed greater adherence to the PMN monolayers than did light SS-RBC (P < .001). To determine mechanisms of this adhesion, IgG and Arg-Gly-Asp-Ser (RGDS) receptor sites on PMN were saturated. IgG inhibited adherence of dense SS-RBC, whereas RGDS inhibited adherence in both fractions, although to a greater extent in the light fraction. We measured SS-RBC activation of PMN by incubating SS-RBC with 2', 7'-Dichloro-fluroescin Diacetate (DCF)-labeled PMN. Incubation of PMN with SS-RBC resulted in a significant increase in fluorescence compared to AA-RBC. We show here that PMN recognize SS-RBC through multiple mechanisms and that this recognition results in activation of PMN. These findings contribute to the understanding of vasoocclusive crisis in patients with SCD and may have therapeutic implications.

Changes in micturition volume thresholds in conscious dogs following spinal opiate administration.

Micturition difficulties appear as an often-reported side effect of the clinical use of opiates for spinal analgesia. Only a few experimental studies have focused specifically on this problem, especially in an unanesthetized animal model where chronic pharmacological studies can be carried out. The changes in micturition volume thresholds that occurred following spinal intrathecal injections of 1 mg of morphine sulphate were measured in 11 conscious dogs and compared with threshold changes produced in these same dogs by i.v. injections of various doses of morphine sulphate and by intrathecal and i.v. injections of naloxone HCl. In all cases, intrathecal or systemic morphine at doses of 1.0 mg or greater significantly (P less than 0.05) increased the bladder volume at which micturition took place. Naloxone, injected intrathecally to reverse the effects of intrathecal morphine, significantly reduced the micturition volume threshold, in most cases to below control volumes. A 400 microgram dose of naloxone, injected intrathecally without prior injection of morphine, significantly lowered the volume threshold in 9 dogs, even though two of these dogs had elevated thresholds following naloxone injection. The reduction in volume thresholds by i.v. naloxone not preceded by morphine injection was not statistically significant over that of control. These results are interpreted in light of recent findings concerning localization of endogenous opiate receptors within the micturition reflex pathway.