TL;DR: It is anticipated that different diseases associated with glomerular sclerosis will be found to depend to varying extents on these two potential mechanisms of sclerosis: the capacity of both intrinsic cells and infiltrating cells to alter the microenvironment of the glomerulus so that sclerosis progresses inexorably long after the disappearance of the initiating insult.
TL;DR: It was noted that indicator sheep erythrocytes densely coated with the third component of complement (C3) specifically adhered to all of the glomeruli in the tissue sections of human kidney, suggesting the presence of a receptor for C.
Abstract: In the course of studying the nature of mononuclear cellular infiltrates in tissue sections of human kidney it was noted that indicator sheep erythrocytes densely coated with the third component of complement (C3) specifically adhered to all of the glomeruli in the tissue sections. The deposition of complement (C) within the glomerulus is a feature of many immunologically related renal diseases (1,2), yet the precise mechanism by which C is deposited remains unexplained. We feel that this observation, suggesting the presence of a receptor for C, is, therefore, of particular interest.
TL;DR: A previously unknown form of multicellular intravascular patrolling that involves both monocytes and neutrophils is described, which may underlie the susceptibility of the glomerulus to inflammation.
Abstract: In contrast with many capillary beds, the glomerulus readily supports leukocyte recruitment. However, little is known regarding the actions of leukocytes following their recruitment to glomeruli. We used multiphoton confocal microscopy to examine leukocyte behavior in the glomerular microvasculature. In normal glomeruli, neutrophils and monocytes were retained in capillaries for several minutes, remaining static or migrating intravascularly. Induction of glomerular inflammation resulted in an increase in the duration of retention of static and migratory leukocytes. In response to immune complex deposition, both static and migratory neutrophils generated oxidants in inflamed glomeruli via a Mac-1-dependent mechanism. Our results describe a new paradigm for glomerular inflammation, suggesting that the major effect of acute inflammation is to increase the duration of leukocyte retention in the glomerulus. Moreover, these findings describe a previously unknown form of multicellular intravascular patrolling that involves both monocytes and neutrophils, which may underlie the susceptibility of the glomerulus to inflammation.
TL;DR: In the coming decade, the use of global expression profiling platforms, transgenic mouse lines, and other in vivo gene delivery methods will rapidly expand the understanding of biology and pathology of the glomerular filtration barrier, and hopefully expose novel target molecules for therapy in progressive renal diseases.