R. NEAL PINCKARD, Ph.D.
Professor of Pathology and Medicine

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Department of Pathology – Mail Code 7750
The University of Texas Health Science Center
7703 Floyd Curl Drive
San Antonio, Texas 78229-3900
INFORMATION
Email: pinckard@uthscsa.edu
Phone: (210) 567-4070   Fax: (210) 567-2303


EDUCATION
1963 B.A., University of Kansas
1967 Ph.D., University of Edinburgh Medical School, Edinburgh, Scotland
 
TRAINING
1967-68 Postdoctoral Fellowship in Allergy, Immunology and Rheumatology. Scripps Clinic and Research Foundation, La Jolla, California


PROFESSIONAL SOCIETY MEMBERSHIPS
1. American Society for Investigative Pathology
2. Society for Leukocyte Biology
3. Inflammation Research Association


DESCRIPTION OF RESEARCH
    Our research interests have focused on characterizing the pathophysiology of several choline-containing phospholipid inflammatory mediators collectively known as platelet-activating factors (PAF). Most recently we have been elucidating the role that surface associated vascular endothelial cell PAF may play in the adherence and juxtacrine activation of human neutrophils (PMN). First passage human umbilical cord endothelial cells (HUVEC) that are stimulated with several different agonists (including thrombin, histamine, ATP, hydrogen peroxide) synthesize small amounts (~ 2 pmoles) of alkyl-PAF (1-O-alkyl-2-acetyl-sn-glycero-3-phosphocholine) and appreciable quantities (> 30 pmoles) of acyl-PAF (1-acyl-2-acetyl-sn-glycero-3-phosphocholine), 18% of which is expressed on the HUVEC surface. In contrast, stimulation of the same HUVEC isolates with two, potent inflammatory cytokines (TNF? or IL-1?) does not induce the production of any detectable alkyl-PAF or acyl-PAF (< 0.1 pmole); surprisingly however, at least 40% of the enhanced PMN adherence to these TNF?- or IL-1?-stimulated HUVEC is PAF-dependent. This is because the PMN adherence to the cytokine-stimulated HUVEC is blocked either by a specific PAF receptor antagonist (WEB 2086) or by a human recombinant PAF degradative enzyme (PAF acetylhydrolase, which hydrolyzes the short-chain sn-2 fatty acyl constituent of PAF). Thus, since the both the PMN PAF receptor (WEB 2086 inhibition) and a PAF-like molecule (PAF acetylhydrolase sensitive inhibition) are involved in a significant proportion of TNF?-induced PMN adherence, we believe that other PAF-like molecules must be produced by cytokine-stimulated HUVEC. Therefore, our current objective is to structurally elucidate the chemical nature(s) of and the pathway(s) that are involved (chemical/enzymatic) in the production of these PAF-like molecules produced by cytokine (TNF?- or IL-1?)-stimulated HUVEC.


SELECTED PUBLICATIONS
1. Woodard, D.S., Mealey, B.L., Lear, C.S., Satsangi, R.K., Prihoda, T.J., Weintraub, S.T., Pinckard, R.N., and McManus, L.M.: Molecular Heterogeneity of PAF in Normal Human Mixed Saliva: Quantitative Mass Spectral Analysis After Direct Derivatization of PAF with Pentafluorobenzoic Anhydride. Biochim. Biophys. Acta. 1259:137-147 (1995).

2. Pinckard, R.N. and Prihoda, T.J.: Alkyl-PAF and Acyl-PAF Human Neutrophil Priming for enhanced FMLP and rC5a Induced Superoxide Anion Production. J. Leuk. Biol. 59:219 228 (1996).

3. Pinckard, R.N., Woodard, D.S., Weintraub, S.T. and McManus, L.M.: Qualitative and Quantitative Assessment of Platelet-Activating Factors. In Handbook of Experimental Pharmacology. Platelets and their Factors, FV Bruchhausen and U Walter, Eds, Springer-Verlag, Heidelberg 126:507-527, (1997).

4. McManus, L.M. and Pinckard, R.N.: PAF, A Putative Mediator of Oral Inflammation. Crit. Rev. Oral Biol. 11:240-258 (2000).

5. Weintraub S.T., Satsangi R.K., Sprague E.S., Prihoda, T.J., and Pinckard R.N.: Mass Spectrometric Analysis of Platelet-Activating Factor after Isolation by Solid Phase Extraction and Direct Derivatization with Pentafluorobenzoic Anhydride. J. Amer. Soc. Mass Spectrom. 11:176-181 (2000).

6. McManus, L.M., Bloodworth, R.C., Prihoda, T.J., Blodgett, J. and Pinckard, R.N.: Agonist-Dependent Failure of Neutrophil Function in Diabetes Correlates with Extent of Hyperglycemia. J. Leuk. Biol. 70:395-404, 2001.

Updated on 04/17/2002