Both Classical and Non-Classical Monocytes Patrol Glomerular Capillaries and Promote Acute Glomerular Inflammation

Tan, Zhehao and Hall, Pam and Mack, Matthias and Snelgrove, Sarah L. and Kitching, A. Richard and Hickey, Michael J. (2025) Both Classical and Non-Classical Monocytes Patrol Glomerular Capillaries and Promote Acute Glomerular Inflammation. AMERICAN JOURNAL OF PATHOLOGY, 195 (1). pp. 89-101. ISSN 0002-9440, 1525-2191

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Abstract

Monocyte patrolling of the vasculature has been ascribed primarily to the non-classical monocyte subset. However, a recent study of the glomerular microvasculature provided evidence that both classical and non-classical monocytes undergo periods of intravascular retention and migration. Despite this, whether these subsets contribute differentially to acute glomerular inflammation is unknown. This study used glomerular multiphoton intravital microscopy to investigate the capacity of classical and non-classical monocytes to patrol the glomerular microvasculature and promote acute, neutrophil-dependent glomerular inflammation. In imaging experiments in monocyte reporter Cx3cr1(gfp/+) mice, co-staining with anti-Ly6B or anti-Ly6C revealed that both non-classical monocytes [CX3 chemokine receptor 1-green fluorescent protein positive (CX3CR1-GFP(+))] and classical monocytes (CX3CR1-GFP(+) and Ly6B(+) or Ly6C(+)) underwent prolonged (>10 minutes) retention and migration in the glomerular microvasculature. On induction of acute glomerulonephritis, these behaviors were increased in classical, but not non-classical, monocytes. Using non-classical monocyte-deficient Csf1r(Cre)Nr4a1(fl/fl) mice, or anti-CCR2 to deplete classical monocytes, the removal of either subset reduced neutrophil retention and activation in acutely inflamed glomeruli, while the depletion of both subsets, via anti-CCR2 treatment in Csf1r(Cre)Nr4a1(fl/fl) mice, led to further reductions in neutrophil activity. In contrast, in a model of CD4(+) T cell-dependent glomerulonephritis, the depletion of either monocyte subset failed to alter neutrophil responses. These findings indicate that both classical and non-classical monocytes patrol the glomerular microvasculature and promote neutrophil responses in acutely inflamed glomeruli.

Item Type: Article
Uncontrolled Keywords: LEUKOCYTE RECRUITMENT; CCR2(+) MONOCYTES; SUBSETS; GLOMERULONEPHRITIS; MACROPHAGES; REVEALS; CELLS; NEUTROPHILS; RECEPTOR; INJURY;
Subjects: 600 Technology > 610 Medical sciences Medicine
Divisions: Medicine > Lehrstuhl für Innere Medizin II
Depositing User: Dr. Gernot Deinzer
Date Deposited: 24 Mar 2026 09:13
Last Modified: 24 Mar 2026 09:13
URI: https://pred.uni-regensburg.de/id/eprint/64813

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