Annexin I Is a Local Mediator in Neural-Endocrine Feedback Control of Inflammation

Author:

Green Paul G.12,Strausbaugh Holly J.123,Levine Jon D.142

Affiliation:

1. Department of Oral and Maxillofacial Surgery,

2. Division of Neuroscience and National Institutes of Health Pain Center, and

3. Biomedical Sciences Program, University of California San Francisco, San Francisco, California 94143-0440

4. Department of Medicine,

Abstract

Green, Paul G., Holly J. Strausbaugh, and Jon D. Levine. Annexin I is a local mediator in neural-endocrine feedback control of inflammation. J. Neurophysiol. 80: 3120–3126, 1998. Activation of primary afferent nociceptors induces a neural endocrine–mediated inhibition of the inflammatory response via a circuit that includes ascending spinal pathways and activation of the hypothalamic-pituitary adrenal (HPA) axis. This circuit inhibits sympathetic neuron-dependent plasma extravasation (PE) in the rat knee joint produced by bradykinin (BK), but not sympathetic neuron–independent PE produced by platelet activating factor (PAF). Noxious (25 mA) but not non-noxious (2.5 mA) electrical stimulation significantly increased plasma corticosterone concentrations, and intravenous infusion of corticosterone (5 μg/min) mimicked inhibition of BK-induced PE produced by noxious stimulation. However, perfusion of corticosterone locally through the knee joint, at doses that do not have a systemic action (i.e., ≤1 μM), did not inhibit BK-induced PE. Annexin I (lipocortin-1), a 37-kDa member of a family of phospholipid and calcium binding proteins, can mediate local anti-inflammatory effects of glucocorticoids via a mechanism that is partially dependent on inhibition of phospholipase A2 activity and adhesion and transmigration of polymorphonuclear leukocytes. Because BK-induced PE is dependent on both polymorphonuclear leukocytes and phospholipase A2 activity, we tested the hypothesis that the action of corticosterone to inhibit BK-induced PE is mediated by stimulating the production and release of annexin I. Perfusion of BK (150 nM) through the rat knee joint induces a rapid and sustained increase in PE. Co-perfusion of BK with annexin I (100 ng/ml) through the knee joint mimics the inhibition of BK-induced PE produced by noxious electrical stimulation or by intravenous corticosterone. Co-perfusion of BK with annexin I antibody (LCPS1, 1:60 dilution) prevented the inhibition of BK-induced PE produced by noxious electrical stimulation or intravenous corticosterone adminstration. PAF-induced PE, which is not dependent on polymorphonuclear leukocytes, was not inhibited by local perfusion of annexin I. These data suggest that the inhibitory effect of C-fiber activity on BK-induced PE, acting via an HPA circuit, is mediated by annexin I in the knee joint.

Publisher

American Physiological Society

Subject

Physiology,General Neuroscience

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