A critical host defense mechanism in response to bacterial infection or tissue injury is an influx of polymorphonuclear neutrophilic leukocytes, or neutrophils, to the affected area. Once at the inflamed site, the neutrophils ingest, or phagocytose, bacteria or damaged tissue and release toxic oxygen metabolites (O2H2O2) and proteolytic enzymes to digest the phagocytosed material. Activation of these neutrophils is initiated by local production of compounds known as chemoattractants, either by the body or the invading bacteria. Similarly, bacteria that have been “tagged” by antibodies binding to their surface also provoke activation of neutrophils. However, in autoimmune diseases in which the body “tags” its own tissue with antibodies, this response becomes pathologic as the neutrophils trigger inappropriate inflammation.
We study the intracellular signals produced by neutrophils after activation by chemoattractants, aggregated immune complexes, and antibody-coated particles. We …have used a unique protein produced by Neisseria gonorrhoea (Por) as a probe to dissect which signals are requried for the idscrete responses of chemotaxis, O2 generation, and lysosomal enzyme release. Pretreatment of neutrophils with Por inhibits the release of granule enzymes triggered by chemoattractants and, in parallel, inhibits the production of the diglyceride class of second messengers. Interestingly, Por does not inhibit neutrophil function triggered by immune complexes thus indicating that chemoattractants and immune complexes activate different signaling pahtways. We continue to examine the relationship of other signals such as protein kinases, phosphatases, and lipid products to neutrophil function in bacterial infection and pathologic inflammation to help us understand and control this important aspect of both health and disease.
Dr. Kathleen Ann Haines, MD
Dr. Kathleen Ann Haines, MD
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Medical School
- 1975
Albert Einstein College Of Medicine Of Yeshiva University
Hackensack University Medical Center
30 Prospect Ave
Hackensack
NJ
07601
USA
+15519965430
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