Systemic evaluation and localization of resistin expression in normal human tissues by a newly developed monoclonal antibody

Abstract

Resistin and resistin-like molecules are pleiotropic cytokines that are involved in inflammatory diseases. Our previous work suggested that resistin has the potential to be used as a biomarker and therapeutic target for human pulmonary arterial hypertension. However, data are limited on the distribution of resistin in healthy human organs. In this study, we used our newly developed anti-human resistin (hResistin) antibody to immunohistochemically detect the expression, localization, and intracellular/extracellular compartmentalization of hResistin in a full human tissue panel from healthy individuals. The potential cross reactivity of this monoclonal anti-hResistin IgG1 with normal human tissues also was verified. Results showed that hResistin is broadly distributed and principally localized in the cytoplasmic granules of macrophages scattered in the interstitium of most human tissues. Bone marrow hematopoietic precursor cells also exhibited hResistin signals in their cytoplasmic granules. Additionally, hResistin labeling was observed in the cytoplasm of nervous system cells. Notably, the cytokine activity of hResistin was illustrated by positively stained extracellular material in most human tissues. These data indicate that our generated antibody binds to the secreted hResistin and support its potential use for immunotherapy to reduce circulating hResistin levels in human disease. Our findings comprehensively document the basal expression patterns of hResistin protein in normal human tissues, suggest a critical role of this cytokine in normal and pathophysiologic inflammatory processes, and offer key insights for using our antibody in future pharmacokinetic studies and immunotherapeutic strategies.

Resistin Associated With Cytokines and Endothelial Cell Adhesion Molecules Is Related to Worse Outcome in COVID-19

“…Several mechanisms of resistin secretion in sepsis have been reported ( 33 , 34 ), but the mechanism in COVID-19 has remained unclear. In humans, resistin is delivered from peripheral blood mononuclear cells, macrophages and bone marrow rather than from adipocytes ( 2 , 35 , 36 ). In the present study, resistin gene expression in whole blood cells was elevated, suggesting that these cells were responsible for the production of resistin in COVID-19 patients.…”

Resistin Forms A Network With Inflammatory Cytokines And Endothelial Damage Markers And Provides Prognostic And Therapeutic Information For COVID-19

“…In humans, resistin is delivered from peripheral blood mononuclear cells, macrophages and bone marrow, rather than from adipocytes [12,22,23]. In the present study, the resistin gene expression in whole blood cells was elevated, suggesting that these cells were responsible for the production of resistin in COVID-19 patients.…”

Generation of a humanized afucosylated BAFF-R antibody with broad activity against human B-cell malignancies

“…The tissue cross-reactivity study of the H90-5 Ab was performed with autopsy archival tissues from 3 healthy humans using the avidin-biotin immunoperoxidase method, as described previously. 17 In total, 35 human organs were examined, and the primary Ab was H90-5 or human IgG1κ used at concentrations of 2 μg/mL and 10 μg/mL. Positive tissue staining was verified with an anti–β2-microglobulin Ab.…”