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Microcirculation

Microcirculation

Dr Felicity N. E. Gavins

Principal Investigator, CIMPP Research Lecturer

A hallmark of inflammation is the mobilization of blood-borne leukocytes across microvessels to kill and remove the invading pathogen. Despite leukocyte movement being tightly regulated, it is associated with the pathogenesis of a number of inflammatory disease states such as stroke and myocardial infarction.

An important area of research is leukocyte-platelet-endothelial cell interactions and their involvement in both inflammation and ischaemia reperfusion injury. Direct observation of an inflamed microcirculation has allowed the characterization of the leukocyte transmigration process, which has lead to distinct steps being defined: cell rolling, adhesion and emigration (Figure 1). Leukocyte transmigration is itself a protective process that the host sets up to control pathogen invasion and other insults. However, under certain conditions, this process can be detrimental to the host due to the production and release of a cocktail of toxic chemicals.

schematic

Disease states such as stroke and myocardial infarction are connected to a variety of risk factors, including hypercholesterolemia, diabetes and hypertension. Features of the inflammatory response that are common to many of these pathological conditions and that are manifested in the vasculature include oxidative stress, diminished endothelial barrier function (increased vascular permeability), increased expression of endothelial cell adhesion molecules, and the recruitment of rolling and adherent leukocytes and platelets. Evidence has implicated leukocyte-endothelial cell adhesion in microvessels as a rate-determining component of the pathophysiology associated with conditions such as ischemia-reperfusion and sickle cell disease.

There are many structural and functional characteristics of the cerebral microvasculature that distinguish it from other regional vascular beds. However, the processes that underlie the recruitment of injury-causing inflammatory cells in the brain appear to closely resemble those described for other tissues and this is the main focus of our research.

To address research objectives, the specialised technique of intravital microscopy is utilised. This enables the microcirculation to be visualised in real time (see Movie 1 and figures 1 & 2), thus facilitating the quantification cellular interactions with the endothelium.

Fig1

Figure 1. Visible alterations in the microcirculation following ischaemia reperfusion (IR) of the superior mesenteric artery. Alterations seen with FITC-labeled albumin in vessels with no inflammation (A: normal light, C: fluorescence) & those that have undergone ischemia reperfusion (B: normal light, D: fluorescence): Gavins et al., Blood. 2003;101:4140-7.

Fig2

Figure 2: An example of an inflamed murine mesenteric post capillary venue.

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