LINDA M. McMANUS, Ph.D. Professor Phone (voice): 210 567 4071 E-mail: mcmanus@uthscsa.edu

Degrees

1978, Ph.D., University of Colorado Medical School
1973, M.S., University of Houston
1970, B.S., University of Texas at Austin

Postdoctoral Training

1978-80, Department of Pathology, University of Texas Health Science Center at San Antonio

Description of Research

    Diabetes is associated with diminished inflammatory cell function and infections. However, the mechanism(s) underlying deficits in inflammatory cell function in diabetes remain poorly understood. Our on-going studies have demonstrated that there are significant hyperglycemia-associated decreases in the functional responsiveness of human neutrophilic polymorphonuclear leukocytes (PMN), but only in response to agonists that initiate signal transduction through G-protein-coupled receptors (GPCR). That is, cellular responsiveness to other stimuli (non-GPCR) by diabetic PMN is normal. Thus, current studies are focused on elucidating the basis for GPCR-selective cellular dysfunction in diabetic PMN. Primary efforts are directed towards defining alterations in intracellular signal transduction that contribute to the decreased functional phenotype of diabetic PMN in relation to the extent of hyperglycemia. To address this goal, PMN are isolated from the peripheral blood of human subjects with diabetes mellitus; these cells are then assessed in vitro. It is anticipated that these investigations will provide important, novel information regarding agonist-selective and hyperglycemia-associated PMN dysfunction in diabetes. These details may be useful in the treatment or prevention of diabetic infections and compromised inflammatory responses.

Selected References

McManus LM, Woodard DS, Deavers SI, Pinckard RN. PAF molecular heterogeneity: Pathobiological implications. Lab Invest 69:639-650, 1993.

Pinckard RN, Woodard DS, Showell HJ, Conklyn MJ, Novak MJ, McManus LM. Structural and (patho) physiological diversity of PAF. Clin Rev Allergy 12:329-359, 1994.

Woodard DS, Ostrom KK, McManus LM. Lipid inhibitors of platelet activating factor (PAF) in normal human plasma. J Lipid Med Cell Signaling 12:11-28, 1995.

Woodard DS, Mealey BL, Lear CS, Satsangi RK, Prihoda TJ, Weintraub ST, Pinckard RN, McManus LM. 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.

Pinckard RN, Woodard DS, Weintraub ST, and McManus LM. Qualitative and quantitative assessment of platelet activating factors. In Handbook of Experimental Pharmacology, Vol 125. Platelets and Their Factors, F.V. Bruchhausen and U. Walter, editors, Springer-Verlag, Heidelberg, pp. 507-527 (1997).