Immune cells bandage wounds
Neuophils aid in wound healing by releasing extracellular matrix and other toxins, as observed in mouse skin, lungs and intestinal organs by atomic force microscopy
Scientists have long known that neutrophils wage chemical warfare by releasing toxins to kill invading microorganisms. According to a clinical immunologist who wasn’t involved in the study, the new work shows an additional role for the neutrophils that we had not appreciated. The findings show that neutrophils aid in wound healing — and are not just immune warriors, she adds.
The researchers examined samples of mouse skin, lungs and gut organs that are lined with protective layers to help ward offbacteria and foreign substances, in order to see if the neutrophils have another trick up their sleeves. Hidalgo and his colleagues found that a high percentage of neutrophils in these tissues produce collagen and other proteins that are important for forming ‘extracellular matrix’, a scaffolding that surrounds cells and gives tissues structure. By contrast, neutrophils in blood did not release collagen.
Representations of the neutrophils stained for Col3a1 in their skin in the WT control, as well as images from 2 mice, and TgfbrN mice. Mean values are presented when compared by two-tailed unpaired Student’s test. b, Histological characterization of the skin of wild-type control (n = 3) and TgfbrΔN mice (n = 3) by hematoxylin-eosin staining for cell and tissue structure, Masson’s trichrome for collagen-rich structures, and Ki67 staining for dermal and epidermal proliferation. The dot plot graphs show the quantified images. P-values were determined by a two-sided unpaired Student’s t-test. The diagram below shows the distribution of width in the histogram, as well as the examples of fibre reconstruction usingCT-FIRE. iDTR mice are better than control mice. Two-sided student t-tests were used to determine P-values. d, Schematics of the atomic force microscopy (AFM) set-up used to measure the stiffness of tissue samples (left) and its quantification in the form of elastic Young’s modulus in lung, intestine and skin of CreNEG;Tgfbrflox control (referred to here as WT; n = 5) and TgfbrΔN littermates (n = 5 mice). Each dot represents the median Young’s modulus value calculated from ∼250 individual force–distance analysed curves per mouse. Data were compared by two-sided unpaired Student’s t-test. Right, representative height images and corresponding Young’s modulus maps of skin from control (n = 5) and TgfbrΔN littermates (n = 5) acquired by AFM indentation experiments. The ear skin is shown in the images of the ear skin to be the sub epidermis and lower dermis regions. Yellow circles highlight large collagen fibres (>0.2 μm2) in the subepidermal region. Data from 2 independent experiments show that fibre size can be determined in the skin of TgfbrN mice. P-values determined by Kruskal-Wallis non-parametric test. The mean values were presented and the p-values were determined with a non-parametric test. h, Permeability assays in control (n = 7) and TgfbrΔN mice (n = 7) measured by FITC–dextran injected either intratracheally (for lung), or by oral gavage (for gut) in CreNEG control (n = 8) and TgfbrΔN mice (n = 8). Evans blue given intravenously to control (n = 11) and TgfbrΔN mice (n = 5) and then measured in the indicated tissues. There were Cre- negative Tgfbrflox littermates here. i,j, Stiffness (i) and permeability assay (j) using Evans blue in the ear skin of Mrp8Cre; Tgfbr2flox and Ly6GCre; Tgfbr2flox mice, as well as CreNEG; Tgfbr2flox littermates, or mice treated with anti-Ly6G to deplete neutrophils or isotype control antibody. The numbers of replicates are displayed in the figure. One-way ANOVA with multiple comparison test is used to compare each method with their controls. Box plots in (d,h–j) show median ± interquartile; whiskers show the range from minimum to maximum. Box plots in f show median ± interquartile; whiskers are defined with percentiles and IQR (interquartile range, P75–P25); the points outside this range are the outliers.
Neuophils aid in wound healing by releasing extracellular matrix and other toxins, as observed in mice skin, lungs and intestinal organs by atomic force microscopy. The neutrophils stained for Col3a1 in their skin in WT control, as well as images from 2 mice, and TgfbrN mice. Further, independent experiments showed that fibre size can be determined in the skin of TgfbrN mice.