Recognition and uptake of human diabetic peripheral nerve myelin by macrophages

H. Vlassara, M. Brownlee, A. Cerami

Research output: Contribution to journalArticlepeer-review

74 Scopus citations

Abstract

Macrophages recognize and ingest several human proteins whose amino groups have been modified in vitro by specific chemical reagents. Because amino groups of human peripheral nerve myelin proteins become covalently modified in vivo by products of nonenzymatic glycosylation, we examined myelin/macrophage interactions using peripheral nerve myelin prepared from diabetic and nondiabetic patients. Intracellular accumulation of diabetic myelin increased with concentration in an apparently saturable fashion, reaching levels 3-4 times higher than those of age-matched nondiabetic samples. Low-temperature inhibition of cellular myelin accumulation further suggested that diabetic myelin uptake was associated with absorptive endocytosis. Macrophage recognition and accumulation of nondiabetic myelin glycosylated in vitro increased with duration of sugar incubation, to a level nearly nine times that of the same sample incubated in buffer alone. Data from competition experiments with albumin and myelin glycosylated in vitro showed that recognition of human peripheral nerve myelin proteins by macrophages is specific for protein-bound products of nonenzymatic glycosylation. In vivo, such macrophage recognition of and interaction with nonenzymatic glycosylation products on diabetic peripheral nerve myelin could contribute to the pathogenesis of segmental demyelination.

Original languageEnglish (US)
Pages (from-to)553-557
Number of pages5
JournalDiabetes
Volume34
Issue number6
DOIs
StatePublished - 1985
Externally publishedYes

ASJC Scopus subject areas

  • Internal Medicine
  • Endocrinology, Diabetes and Metabolism

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