Other connective tissue macromolecules

Fibronectin, a major regulator of cell attachment to the ECM and overall cell morphology, has recently been shown to be fragmented after exposure to HO [27] while exposure to OC1- resulted in substantial cross-linking (bityrosine cross-links) [28], Exposure of fibronectin to either of these oxidants led to the formation of dysfunctional biomolecules and may provide a rational explanation for the frequently observed detachment of endothelial or epithelial cells seen during connective tissue injury. The presence of these modified forms of fibronectin in the ECM adjacent to an inflammatory focus would provide strong evidence for the role of oxidant-induced connective tissue damage, but this information is not currently available. 

The evidence for a pathophysiological role of oxidants in connective tissue injury is not confined to oxidative damage to the component macromolecules. Since there is reasonable indirect evidence that ROIs are released into the articular joint space during inflammation, it is likely that ROIs released from inflammatory cells which are adherent to or in contact with the articular cartilage surface might also damage the cellular components of articular cartilage. 

All the major cell types (epithelial, endothelial, smooth muscle cells, pneumocytes, chondrocytes, fibroblasts) capable of producing connective tissues (e.g. cartilage, basement membrane, parenchymal stroma) are susceptible to oxidative injury in vitro [29- 33], and over the past decade the mechanism(s) of oxidative stress to these cell types has been the focus of intense research. Unfortunately, few of these studies have been specifically extended to examine the biochemical evidence for oxidative injury to connective tissue producing cells in vivo [34], Our most recent work has concentrated on determining the precise biochemical footprints of oxidative injury found within chondrocytes (also colonic epithelial cells) and attempting to correlate the presence or absence of these oxidative-injury markers seen in vitro with inflamed material from animal models and human pathological material. 

Exposure of various cells to ROIs (H2O2, OC1-) in vitro causes a multitude of biochemical alterations including (a) loss of intracellular ATP and NAD+, (b) stimulation of HMP shunt activity, (c) DNA strand breakage, (d) increase in oxidized protein thiol groups, (e) increase in intracellular Ca2+, (f) activation of poly(ADP-ribose) polymerase, (g) alterations in cell morphology, (h) inhibition of many biosynthetic pathways, (i) 51Cr release, (j) intracellular enzyme 

In conclusion, the evidence for the involvement of ROIs in injury to the cellular components of connective tissues is stronger than that of direct macro-molecular damage because some of the footprints of in vitro oxidative injury have been found in animal models of inflammation and from human pathological material pathological material. 

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Numerous studies have shown that exposure of connective tissue macromolecule substrates (hyaluronic acid, collagens, elastin, proteoglycans, laminins, fibronectins and vitronectins) to HO causes substantial degradation of these substrates. Fewer studies have examined the possibility that other ROIs (e.g. OC1-, chloramines, peroxides) may be involved in connective tissue macromolecule damage. Even fewer researchers have attempted to identify the... 

Fibroblasts Connective tissue cells which secrete an extracellular matrix rich in collagen and other macromolecules, [nih]... 

At the present time, it is known that HA is not an inactive macromolecule of connective tissue, but a metabolically highly active biopolymer. Its half-life in the joints is 1-30 weeks, up to 1-2 days in the epidermis and derma and only 2-5 minutes in the bloodstream. In other words, during one day, approximately 5 g of dry HA can be synthesized and cleaved in the body of an adult 70-kg man, one-third of the whole amount of HA in the body [17]. 

Lignins usually comprise between 25 and 30% wt/wt of woody tissues in hardwoods and softwoods, respectively. Unfortunately, they cannot be removed from the constituent cell walls without concomitant degradation. In this connection difficulties are invariably encountered because the majority of interunit linkages in lignin macromolecules are relatively stable, much more so than those in most other biopolymers. Thus isolated lignin preparations differ from one another in the extent to which they have been modified with respect to the native macromolecules. 

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