Immunohistochemical detection of advanced glycosylation end products in diabetic tissues using monoclonal antibody to pyrraline.

Pyrraline is one of the major Maillard compounds resulting from the reaction of glucose with amino compounds at slightly acidic pH. For in vivo studies, monoclonal pyrraline antibodies were raised after immunization of Balb/c mice with keyhole limpet hemocyamin-caproyl pyrraline conjugate. Of 660 hybridoma clones from one donor, 260 produced an antibody to the free hapten, two of which named Pyr-A and Pyr-B also cross-reacted with L-lysyl pyrraline. Using Pyr-B antibody and an ELISA, a gradual increase in pyrraline immunoreactivity was observed in serum albumin incubated with glucose or 3-deoxyglucosone. Plasma pyrraline levels increased fourfold (P less than 0.001) in Sprague-Dawley rats upon induction of diabetes with streptozotocin and were twofold increased in randomly selected plasmas from diabetic humans. Highly specific pyrraline immunoreactivity was detected in sclerosed glomeruli from diabetic and old normal kidneys as well as in renal arteries with arteriolosclerosis and in perivascular and peritubular sclerosed extracellular matrix and basement membranes. The preferential localization of pyrraline immunoreactivity in the extracellular matrix strengthens the notion that the advanced glycosylation reaction may contribute to decreased turnover and thickening of the extracellular matrix in diabetes and aging.

[1]  C. Kaetzel,et al.  Characterization of a monoclonal antibody to bovine xanthine oxidase. , 1984, The Biochemical journal.

[2]  R. W. Wright,et al.  Enhancement by N-hydroxysulfosuccinimide of water-soluble carbodiimide-mediated coupling reactions. , 1986, Analytical biochemistry.

[3]  A. J. Furth.  The maillard reaction in aging, diabetes and nutrition: edited by John W. Baynes and Vincent M. Monnier, Alan R. Liss, 1989. $85.00 (xvii + 432 pages) ISBN 0 8451 5154 1 , 1990 .

[4]  E. Cagliero,et al.  Increased expression of basement membrane components in human endothelial cells cultured in high glucose. , 1988, The Journal of clinical investigation.

[5]  M. Oimomi,et al.  Glycation of cataractous lens in non-diabetic senile subjects and in diabetic patients. , 1988, Experimental eye research.

[6]  G. Köhler,et al.  A better cell line for making hybridomas secreting specific antibodies , 1978, Nature.

[7]  V. Monnier,et al.  3-(D-Erythro-Trihydroxypropyl)-1-Neopentyl Pyrrole-2-Carboxaldehyde. A Novel Nonenzymatic Browning Product of Glucose , 1987 .

[8]  T. Lyons,et al.  Age-dependent accumulation of N epsilon-(carboxymethyl)lysine and N epsilon-(carboxymethyl)hydroxylysine in human skin collagen. , 1991, Biochemistry.

[9]  V. Monnier,et al.  Detection of D-glucose-derived pyrrole compounds during Maillard reaction under physiological conditions. , 1987, Carbohydrate research.

[10]  F. Hayase,et al.  Polymerization of Proteins Caused by Reaction with Sugars and the Formation of 3-Deoxyglucosone under Physiological Conditions , 1988 .

[11]  V. Monnier,et al.  Aging of proteins: immunological detection of a glucose-derived pyrrole formed during maillard reaction in vivo. , 1989, The Journal of biological chemistry.

[12]  D. Horton,et al.  New route for the synthesis of 3-deoxyaldos-2-uloses , 1971 .

[13]  V. Monnier,et al.  End-stage renal disease and diabetes catalyze the formation of a pentose-derived crosslink from aging human collagen. , 1990, The Journal of clinical investigation.

[14]  J. Baynes,et al.  Oxidation of glycated proteins: age-dependent accumulation of N epsilon-(carboxymethyl)lysine in lens proteins. , 1989, Biochemistry.

[15]  J. Tatum,et al.  Degradation of d-glucose with acetic acid and methylamine☆ , 1970 .

[16]  E. Cagliero,et al.  Overexpression of fibronectin induced by diabetes or high glucose: phenomenon with a memory. , 1990, Proceedings of the National Academy of Sciences of the United States of America.

[17]  A. Michael,et al.  Polyantigenic Expansion of Basement Membrane Constituents in Diabetic Nephropathy , 1983, Diabetes.