Hadassah Medical Center
Publishes on Mast cells and histamine, Urticaria and Related Conditions, Drug-Induced Adverse Reactions. 129 papers and 3.2k citations.
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Ten healthy elderly volunteers (mean age: 78.9) underwent a battery of neutrophil function tests. Resting adherence to endothelium, random and directed migration, phagocytosis-induced chemiluminescence, and granule secretory behavior were all indistinguishable from young healthy controls. However, in vivo delivery of neutrophils into skin abrasions was significantly reduced: 8.4 X 10(5), versus 2.7 X 10(6) in the young. In addition, their neutrophils showed a smaller increase in the surface adhesion glycoprotein CD11 and in adherence to endothelium in response to stimulation with FMLP than did cells from young controls. Inversely, baseline CD11 expression was higher in elderly subjects, suggesting that their cells may have an in vivo defect in mediator responsiveness. Serum immunoglobulin and complement concentrations were also compared. The mean IgM level of 106.3 mg/dl in the elderly was significantly below the 154.4 mg/dl in the young. In contrast, concentrations of C3, C4, and total hemolytic complement were significantly higher in the elderly.
Acute ethanol intoxication inhibits neutrophil delivery to sites of inflammation and, concomitantly, reduces the adhesion of neutrophils to surfaces. The effect of ethanol on several other neutrophil functions required for normal delivery are examined herein. Serum-free neutrophil suspensions showed normal resting adherence to endothelial monolayers in ethanol concentrations up to 1000 mg/dL, but when neutrophils were stimulated by 10(-6)M N-formyl-L-methionyl-L-leucyl-L-phenylalanine (fMLP) to induce hyperadherence, ethanol induced a dose-dependent inhibition that was significant at concentrations greater than or equal to 500 mg/dL. Pretreating the endothelium with ethanol had no effect. Similarly, resting surface expression of the adhesive glycoprotein Mac-1 was unaffected by ethanol, but its up-regulation induced by fMLP was inhibited by 25.5% at 250 mg of ethanol/dL and by 52.3% at 1000 mg/dL. Release of both primary and secondary granule contents after activation showed dose-dependent inhibition, whereas resting granule content and spontaneous release were unaffected. Passive neutrophil deformability was significantly enhanced in 500 mg of ethanol/dL. Thus, ethanol affects several neutrophil delivery functions normally activated by inflammatory stimuli.