Introduction Acute Inflammation and Brief Symptoms Mechanisms: Experimentally Induced Allergic Reactions Clinical Consequences and Treatment Chronic Inflammation Site of the Inflammation in Asthma Cell Survival in Airway Tissues Characteristics of Chronic Inflammation Chronic Inflammation in the Different Forms of Asthma Clinic Consequences Treatment of Exacerbations Onset and Duration of Treatment Remodeling of the Airways Characteristics of Airways Remodeling in Asthma Clinical Consequences Radiographic Findings Treatment and Prevention of Airways Remodeling Conclusions

https://www.atsjournals.org/doi/pdf/10.1164/ajrccm.161.5.9903102

Asthma. From bronchoconstriction to airways inflammation and remodeling.

A chronic inflammatory process is almost invariably associated with tissue damage and healing. Healing results in repair and replacement of dead or damaged cells by viable cells. Repair usually involves 2 distinct processes: regeneration, which is the replacement of injured tissue by parenchymal cells of the same type, and replacement by connective tissue and its eventual maturation into scar tissue. In many instances both processes contribute to the healing response. Chronic inflammatory disease can therefore lead to a wide variety of consequences, from complete or partial restitution of organ structure and function to fibrosis. Asthma is characterized by a chronic inflammatory process of the airways. The ensuing healing process results in structural alterations referred to as a remodeling of the airways. The mechanisms underlying these structural alterations are still largely unknown. They are likely to be heterogeneous, leading-through the highly dynamic process of cell de-differentiation, migration, differentiation, and maturation-to changes in connective tissue deposition and to the altered restitution of airways structure, resulting in mucus gland hyperplasia, neovascularization, fibrosis, and an increase in smooth muscle mass.

Tissue remodeling as a feature of persistent asthma.

Hyaluronan Metabolism in Skin

Objective: Recent observations demonstrated that reactive oxygen species facilitate cartilage degradation. We demonstrated that hydrogen peroxide (H2O2) caused inhibition of proteoglycan synthesis, induction of apoptosis and stimulation of extracellular signal-regulated protein kinase (ERK) of the chondrocytes (Inflamm Res 48: 399-403, 1999). To determine whether activation of ERK is involved in the induction of chondrocyte apoptosis, we examined the signal transduction pathways in this hydrogen peroxide induced apoptosis.¶Design: Bovine articular chondrocytes were cultured. To determine the induction of apoptosis, Annexin V staining and terminal deoxynucleotidyl transferase were used. The activity of caspase-3 was measured using an apopain assay kit. Intracellular Ca2+ imaging was observed after fura2-AM loading.¶Results: Hydrogen peroxide enhanced annexin V positive apoptotic cells and caspase-3 activity, which is an executor of apoptosis. Hydrogen peroxide also enhanced intracellular Ca2+ and preincubation with the intracellular Ca2+ chelator protected chondrocytes against hydrogen peroxide-induced cell apoptosis, indicating that an increase in the cytosolic Ca2+ plays a decisive role in this action. When ERK activity was blocked with geldanamycin and PD098059, increased apoptosis was evident.¶Conclusion: Hydrogen peroxide induces chondrocyte apoptosis via Ca2+ signaling, and ERK is involved in these signal transduction pathways.¶

Hydrogen peroxide induces apoptosis of chondrocytes; involvement of calcium ion and extracellular signal-regulated protein kinase.

Factors related to degradation of articular cartilage in osteoarthritis: a review.

Background In unicompartmental knee arthroplasty (UKA), there is no consensus regarding how to determine the anteroposterior (AP) reference of the tibia. A number of surgeons in Japan perform the sagittal saw cut using the medial intercondylar ridge (MIR) of the tibia according to surgical manuals. However, there is no theoretical basis for this practice. Methods Preoperative computed tomography data from 32 lower limbs of 31 Japanese patients who received UKA were used. First, the angles between the surgical epicondylar axis and the MIR and the substitute AP (sAP) line connecting the medial border of the patellar tendon at the articular surface level and the medial intercondylar tubercle were measured. Next, the mediolateral (ML)/AP ratio of the tibial cut surface was measured when cut parallel to the MIR and sAP line. Finally, the ML/AP ratio of the tibial component was investigated in 4 contemporary UKA implants. Results The MIR and sAP line were externally rotated 94.9° ± 4.1° and 90.4° ± 3.6° relative to the surgical epicondylar axis, respectively. Compared with a cut parallel to the MIR, the mean ML/AP ratio of the cut surface was significantly larger, and the ML/AP ratio was closer to the ML/AP ratio of the components for a cut parallel to the sAP line. Conclusion Obtaining the tibial AP orientation is one of the key steps not only in total knee arthroplasty but also in UKA. The sagittal cut referencing the sAP line provides better AP rotation and fitting of the tibia in UKA than referencing the MIR.

Anteroposterior Rotational References of the Tibia for Medial Unicompartmental Knee Arthroplasty in Japanese Patients

We investigated the characteristics of the histamine H1-receptor in cultured rabbit chondrocytes. Scatchard analysis of [3H]pyrilamine, an H1-antagonist, binding to the chondrocytes revealed a single class of binding sites with KD and Bmax values of 90 +/- 12 nM and 56 +/- 11 fmol/10(4) cells, respectively. H1-agonists stimulated the production of keratan sulfate in a dose-dependent manner. Stimulation of keratan sulfate production was inhibited by pyrilamine. Protein kinase C inhibitors (sphingosine and H-7) also had inhibitory effects. Phorbol 12,13-dibutyrate, a direct activator of protein kinase C, activated the production. When protein kinase C in the chondrocytes was down-regulated by preincubation with phorbol ester, the effect of the H1-agonist on keratan sulfate production was abolished. These results indicate that the histamine H1-receptor on chondrocytes mediates the accumulation of keratan sulfate production and that protein kinase C is involved in these events.

Histamine H1-receptor-mediated keratan sulfate production in rabbit chondrocytes: involvement of protein kinase C.

Secretion of hyaluronic acid from synovial fibroblasts is enhanced by histamine: a newly observed metabolic effect of histamine.

We obtained evidence for the presence of a single class of histamine H2 receptor on rabbit chondrocytes. Stimulation of these receptors with specific H2 agonists led to an inhibition of keratan sulfate secretion and rapid (15 min) accumulation of intracellular adenosine 3',5'-cyclic monophosphate (cAMP). Factors such as prostaglandin E2 and parathyroid hormone, which stimulate short-term increases in cAMP, also caused a reduction in keratan sulfate secretion. Conversely, cholera toxin and forskolin, which enhance cAMP accumulation over 48 and 4 h, respectively, as well as a continuous exposure to dibutyryl cAMP, stimulated keratan sulfate secretion. These data suggest that intracellular cAMP must be kept above a certain level for a prolonged period to stimulate keratan sulfate secretion. We conclude that inhibition of keratan sulfate secretion is coupled with activation of the H2 histamine receptor.

Histamine H2 receptor mediates keratan sulfate secretion in rabbit chondrocytes : role of cAMP

Keratan sulfate (KS) is one of the major glycosaminoglycans in cartilage matrix proteoglycan. We find that exogenously added KS totally blocks keratanase sensitive glycosaminoglycan release measured by radiolabeled ligand. We also find that KS release is potentially inhibited by its own presence as measured by ELISA. When KS is digested with keratanase before its addition to the medium, its inhibitory effect on KS secretion is partially blocked. Exogenously added KS promotes the accumulation of the KS epitope in the cell layer. These data suggest that KS negatively regulates its own secretion.

F. Matsumura

Papers

Anteroposterior Rotational References of the Tibia for Medial Unicompartmental Knee Arthroplasty in Japanese Patients

Histamine H1-receptor-mediated keratan sulfate production in rabbit chondrocytes: involvement of protein kinase C.

Secretion of hyaluronic acid from synovial fibroblasts is enhanced by histamine: a newly observed metabolic effect of histamine.

Histamine H2 receptor mediates keratan sulfate secretion in rabbit chondrocytes : role of cAMP

Keratan sulfate inhibits its release in rabbit chondrocyte